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BTS Guideline For Bronchiectasis in Adults
BTS Guideline For Bronchiectasis in Adults
Thorax
An international journal of RESPIRATORY MEDICINE
thorax.bmj.com
BTS Bronchiectasis in Adults Guideline Development Group
The BTS Guideline for Bronchiectasis in Adults has been endorsed by:
Volume 74 Supplement 1
Thorax
Pages 1–69
Section 17
45 Is there any evidence of cross-infection with
pathogenic organisations?
BTS Guideline
What treatments improve outcomes for patients Non- P. aeruginosa colonised patients
with stable bronchiectasis? (see Figure 2 and e. Use azithromycin or erythromycin for patient with bronchi-
Appendix 2 and 3) ectasis. (A)
Recommendations f. Consider inhaled gentamicin as a second line alternative to
➢➢ Consider long term antibiotics in patients with bronchiec- azithromycin or erythromycin. (B)
tasis who experience 3 or more exacerbations per year. (A) g. Consider doxycycline as an alternative in patients intolerant
➢➢ In these patients, the following are recommended of macrolides or in whom they are ineffective. (C)
Step 1 Step 3
• Treat underlying If 3 or more exacerbations/yr
cause despite Step 2*
• Airways clearance Step 2 • 1) If Pseudomonas aeruginosa, Step 4 Step 2
techniques +/– If 3 or more long term inhaled anti- If 3 or more If 5 or more
pulmonary exacerbations/yr pseudomonal antibiotic or exacerbations/yr exacerbations/yr
rehabilitation despite Step 1* alternatively long term macrolide despite Step 3* despite Step 4*
• Annual influenza • 2) If other Potentially Pathogenic
vaccination • Physiotherapy • Long term • Consider regular
Microorganisms, long term
reassessment and macrolide and intravenous
• Prompt antibiotic macrolides or alternatively long term
consider muco- long term inhaled antibiotics every
treatment for oral or inhaled targeted antibiotic
active treatment antibiotic 2-3 months
exacerbations • 3) If no pathogen, long term
• Self management macrolides
plan
*Consider this step if significant symptoms persist despite previous step, even if not meeting
exacerbation criteria
Antibiotics are used to treat exacerbations that present with an acute deterioration (usually over several days) with worsening local symtoms ( cough, increased
sputum volume or change of viscosity, increased sputum purulence with or without increasing wheeze, breathlessness, haemoptysis) and/or systemic upset.
The flow diagram refers to three or more annual exacerbations.
a. Review the patient’s culture and mycobacterial status, Does long term bronchodilator treatment improve outcomes
optimise airway clearance and treat other associated con- for patients with bronchiectasis?
ditions before starting long term antibiotics. Recommendations
b. Prophylactic antibiotics should be only started by respi- ➢ Use of bronchodilators in patients with bronchiectasis and
ratory specialists. co-existing COPD or asthma should follow the guideline
c. Review patients on long term antibiotics six monthly recommendations for COPD or asthma. (D)
with assessment of efficacy, toxicity and continuing need. ➢ Offer a trial of long acting bronchodilator therapy in patients
Monitor sputum culture and sensitivity regularly, al- with symptoms of significant breathlessness. (D)
though in vitro resistance may not affect clinical efficacy. ➢ Reversibility testing to beta 2 agonist or anticholinergic
✓ As adverse event frequency of azithromycin is likely to be bronchodilators may help to identify patients with co-ex-
dose related, 250mg 3 x /week is a pragmatic starting dose isting asthma but there is no evidence to suggest that a
which can then be increased according to clinical response response is required in order to benefit from bronchodila-
and adverse events. tors. (D)
✓ Thresholds for long term treatment may reduce if the
patient is symptomatic between exacerbations and/or Pulmonary rehabilitation
the exacerbations respond poorly to treatment and/or the Recommendations
patient is at high risk of severe exacerbation for example, ➢ Offer pulmonary rehabilitation to individuals who are func-
immunosuppressed. tionally limited by shortness of breath (Modified Medical
✓ Long term antibiotic choice is complex and has to take into Research Council (MMRC) Dyspnoea Scale ≥ 1). (B)
account factors such as tolerance, allergies and sensitivity, ➢ Consider the use of inspiratory muscle training in conjunc-
therefore in some circumstances, other long term antibiotic tion with conventional pulmonary rehabilitation to enhance
regimens may be appropriate (see appendix 3). the maintenance of the training effect. (B)
✓ Perform a suitable challenge test when stable before starting
inhaled antibiotics (see appendix 2)
Good practice points
✓ Consider cyclical IV antibiotics in patients with repeated
✓ Educate all individuals with bronchiectasis on the impor-
infections (≥5/year) despite other treatments.
tance of an exercise training programme.
✓ Alternative inhaled/nebulised agents may become licensed as
✓ Consider the 6 minute walk test (MWT) and/or the incre-
international studies are completed.
mental shuttle walking test (ISWT) when evaluating exercise
✓ For patients receiving long term prophylactic oral antibi-
capacity pre/post pulmonary rehabilitation in bronchiectasis.
otics, the preferred option is to remain on the same antibi-
Prior to this, practice tests should be carried out to eliminate
otic as opposed to monthly rotation of antibiotics. If there is
any learning effect.
a subsequent lack of efficacy, the antibiotic can be changed
✓ Pulmonary rehabilitation providers should offer education
guided by sensitivity results.
sessions tailored to the needs of individuals with bronchiec-
tasis (e.g. airway clearance techniques, the pathophysiology
Research recommendation of bronchiectasis and relevant inhaled therapy).
Long term randomised controlled trials of oral and inhaled anti- ✓ Pulmonary rehabilitation exercise and education sessions
biotics are needed to assess their efficacy and safety in patients should be provided by appropriately qualified health care
with bronchiectasis who have frequent respiratory tract infec- practitioners.
tions with recurrent P. aeruginosa infection or other potential Further information on Pulmonary rehabilitation is provided
pathogenic micro-organisms. in the BTS Quality Standards for Pulmonary Rehabilitation
What is the role of surgery in managing bronchiectasis? Bronchiectasis and other treatments
Recommendations Recommendation
➢➢ Consider lung resection in patients with localised disease ➢➢ Do not routinely recommend alternative treatments (for
whose symptoms are not controlled by medical treatment example cough suppression, nutritional supplementation,
optimised by a bronchiectasis specialist. (D) complementary therapy/homeopathy, supplemental treatments)
➢➢ Offer multidisciplinary assessment, including a bronchi- as part of the management of patients with bronchiectasis. (D)
ectasis physician, a thoracic surgeon and an experienced
anaesthetist, of suitability for surgery and pre-operative
Good practice point
assessment of cardiopulmonary reserve post resection. (D)
✓✓ Record patient’s weight and BMI at each clinic appointment.
Good practice point
✓✓ Consider nutritional support and pre-operative pulmonary Research recommendations
rehabilitation before surgical referral. Further interventional/randomised controlled trials needed to
establish the role of any alternative therapies in the management
Lung transplantation for bronchiectasis of bronchiectasis.
Recommendations Studies assessing the benefits of nutritional supplementation in
➢➢ Consider transplant referral in bronchiectasis patients aged patients with bronchiectasis should be undertaken.
65 years or less if the FEV1 is <30% with significant clin-
ical instability or if there is a rapid progressive respiratory
deterioration despite optimal medical management. (D) Do pathogens have an impact on prognosis
➢➢ Consider earlier transplant referral in bronchiectasis patients in bronchiectasis?
with poor lung function and the following additional factors: Recommendations
massive haemoptysis, severe secondary pulmonary hyperten- ➢➢ Consider patients with chronic P. aeruginosa colonisation at
sion, ICU admissions or respiratory failure (particularly if higher risk of bronchiectasis-related complications. (B)
requiring NIV).(D) ➢➢ Perform regular sputum microbiology screening for patients
with clinically significant bronchiectasis to monitor for
Good practice points pathogens and detect new isolation of P. aeruginosa. (C)
✓✓ Discuss appropriate patients with a transplant centre prior
to formal referral.
What is the evidence for the role of viruses/fungal disease in
✓✓ Optimise management of comorbidities such as osteoporosis
patients with bronchiectasis?
and maintain physical condition through pulmonary rehabil-
Good practice points
itation prior to transplant.
✓✓ Testing to detect viral infection should be considered in
patients with an exacerbation of bronchiectasis.
What is the role of influenza and pneumococcal vaccination in ✓✓ Do not routinely use anti-fungal therapy without evidence
management of bronchiectasis of fungal disease. Fungal cultures can be positive on those
Recommendations receiving long-term antibiotic therapy.
➢➢ Offer annual influenza immunisation to all patients with
bronchiectasis. (D)
➢➢ Offer polysaccharide pneumococcal vaccination to all Does eradication of potentially pathogenic microorganisms
patients with bronchiectasis. (D) improve outcomes in patients with stable bronchiectasis?
Recommendations
➢➢ Offer patients with bronchiectasis associated with clinical
Good practice point deterioration and a new growth of P. aeruginosa (1st isola-
✓✓ Consider influenza vaccination in household contacts of tion or regrowth in the context of intermittently positive
patients with immune deficiency and bronchiectasis to cultures) eradication antibiotic treatment. (first line treat-
reduce the risks of secondary transmission. ment: ciprofloxacin 500–750 mg bd for 2 weeks; second line
✓✓ Consider use of 13 valent protein conjugate pneumococcal treatment: iv antipseudomonal beta-lactam ± an iv amino-
vaccine in patients with bronchiectasis who do not have glycoside for 2 weeks, followed by a 3 month course of nebu-
an appropriate serological response to standard polysac- lised colistin, gentamicin or tobramycin). (D)
charide vaccine (23 valent carbohydrate Pneumococcal ➢➢ Discuss with patients the potential risks and benefits of
vaccine). starting eradication antibiotic treatment versus clinical
Should treatment of bronchiectasis be altered in the presence Antibiotics should only be changed if there is no clinical
of co-morbidities? response.
Recommendations ✓✓ For those on long term antibiotic treatment, there should
➢➢ Consider a trial of inhaled and/or oral corticosteroids in be repeat sensitivity testing where there is a clinical concern
patients with bronchiectasis and inflammatory bowel disease regarding loss of efficacy with therapy.
(IBD). (D)
➢➢ Ensure optimal control of asthma and allergies in patients
Is there any evidence of cross-infection with pathogenic
with both bronchiectasis and asthma (D).
➢➢ Monitor patients with co-morbid COPD and bronchiectasis organisms (conventional bacteria and environmental
as they are at higher risk of death. (D) mycobacteria)?
➢➢ Patients with bronchiectasis and autoimmune conditions Recommendations
should be carefully assessed for autoimmune related lung ➢➢ Individual or cohort segregation based on respiratory tract
disease and often require long term follow up in a secondary microbiology results is not routinely required for patients
care setting. (D) with bronchiectasis. (D)
➢➢ Patients with bronchiectasis who require disease modifying
antirheumatic drugs (DMARDs) or biologics for rheumatoid Good practice points
arthritis should be referred to a chest physician for further ✓✓ Good cross infection prevention principles should be
assessment before treatment is started. (D) applied: seek advice on local policies.
✓✓ The transmissibility of P. aeruginosa in cystic fibrosis appears
more common. In the case of shared facilities with cystic
How should we monitor bronchiectasis? fibrosis patients the cross infection guidelines for cystic
Recommendation fibrosis should prevail.
➢➢ All patients with bronchiectasis should undergo routine
monitoring in order to identify disease progression, path- Research recommendation
ogen emergence and modify treatment where necessary. (D) Large scale robust data that confirm or refute the transmissibility
of key pathogens such as P. aeruginosa and non-tuberculous
Good practice points mycobacteria are needed.
✓✓ Tailor the frequency of routine monitoring to the patient’s
disease severity (see table 7). Specialist vs non-specialist setting
✓✓ Assess patients annually, and more frequently in more severe
Good practice point
disease. ✓✓ Specialist clinics should be considered in patients requiring
✓✓ Perform pulse oximetry to screen for patients who may need hospital follow up.
blood gas analysis to detect respiratory failure.
✓✓ A baseline CXR may provide a useful comparator in the
event of clinical deterioration. What are the complications of bronchiectasis?
Good practice point
✓✓ If haemoptysis 10 mls or less over a 24 hour period, treat
Is there a role for microbiological sensitivity testing? with an appropriate oral antibiotic. If clinical deterioration,
Good practice points arrange emergency admission to hospital.
✓✓ Antibiotic sensitivity testing can be used to determine if ✓✓ Management of major haemoptysis should be multidisci-
resistance develops to either acute or long-term antibiotic plinary with involvement of respiratory physicians, inter-
treatment. ventional radiology and thoracic surgeons. Empirically
✓✓ Where possible, treatment should be guided by antibiotic treat patients with intravenous antibiotic therapy, based on
sensitivity results but is often empirical based on previous their known microbiology, and consider adjunct treatment
sputum bacteriology. with tranexamic acid. Bronchial artery embolisation is the
✓✓ Some patients with an infective exacerbation may respond to recommended first line treatment if significant haemoptysis
antibiotic treatment despite resistance to that drug in vitro. persists.
shown in the evidence tables (++,+or -). The body of evidence Drafting the guideline
for each recommendation was summarised into evidence state- The Guideline Development Group corresponded regularly by
ments and graded using the SIGN grading system (see table 2). email and meetings of the co-chairs sub group and full group
Disagreements were resolved by discussion with the section were held in January, May and June 2014, January, May,
partner. The second literature search in June 2016 yielded 1021 September and December 2015, January, April, December
abstracts. Of these, 277 were identified as definitely or possibly 2016, January and November 2017. A number of teleconfer-
relevant to the guideline. However, of the 277 identified, all ences were also held. The BTS Standards of Care Committee
relevant abstracts from this search had been identified by the (SOCC) reviewed the draft guideline in November 2017. The
Guideline Development Group (GDG) in the intervening time draft guideline was made available on-line March – April 2018
and incorporated. for public consultation and circulated to all the relevant stake-
holders. The BTS SOCC re-reviewed the revised draft guide-
Considered judgement and grading of evidence line in June 2018 and final SOCC approval granted in July
The Guideline Development Group used the evidence tables 2018.
to judge the body of evidence and grade recommendations for This BTS Guideline will be reviewed within 5 years from the
this guideline. Evidence tables (web appendix 3) are available publication date.
online. Where evidence was lacking to answer the formulated
clinical questions, expert opinions were obtained through Guideline group members and declarations of interest
consensus. The following were considered in grading of the All members of the Guideline Group made declarations of
recommendations: interest in line with the BTS Policy and further details can be
The available volume of the body of evidence. obtained on request from BTS. Guideline Development Group
How applicable the obtained evidence was in making recom- members are listed in appendix 1.
mendations for the defined target audience of this guideline.
Whether the evidence was generalisable to the target popu-
lation for the guideline. Stakeholders
Whether there was a clear consistency in the evidence ob- The following organisations contributed to the consultation
tained to support recommendations. exercise:
What the implications of recommendations would be on ACPRC, ARNS, ARTP, BGS, BSTI, Edge Hill University, PCRS-
clinical practice in terms of resources and skilled expertise. UK, ProAxsis Ltd, RCN, RCP Edinburgh, Trudell Medical.
Cost-effectiveness was not reviewed in detail as in-depth
economic analysis of recommendations falls beyond the
scope of this guideline. Section 3
Recommendations were graded from A to D as indicated by How common is bronchiectasis?
the strength of the evidence as shown in table 3. In line with UK data in 2013 revealed the prevalence in women was
SIGN guidance, ‘minus’ evidence was considered in context 566/100 000 and in men 486/100 0004.
but in the absence of other ‘plus’ supporting evidence, it was Data from 12 US states over the period 1993–2006 demon-
discussed among the GDG regarding that point and any recom- strate an average annual age-adjusted hospitalisation rate of
mendation hence made was Grade D. Important practical 16.5 hospitalisations per 1 00 000 population. Women and those
points lacking any research evidence, nor likely to be research aged over 60 years had the highest rate of hospitalisations.2
evidence in the future were highlighted as ‘Good Practice New Zealand hospital admission rates are reported as 25.7 per
Points’ (GPP). 100 0003 highest in childhood and the elderly, and related to
Research recommendations are also provided and the sex, socioeconomic deprivation and race.
overall research questions are presented in PICO format in Regarding co-morbidity coding that may provide information
appendix 8. on aetiology, the UK data found no significant co-morbidity in
Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463 11
BTS Guideline
34% of patients, and the most common coded co-morbidities Using modifications of technique radiation dose of volumetric
to be asthma (42%) and COPD (36%).4 HIV was coded in 7%, CT can be reduced to comparable levels to incremental imaging
rheumatoid arthritis in 6%, other connective tissue disease in while providing higher accuracy. (2+)
5%, inflammatory bowel disease in 3% and antibody deficiency While clearance of inhaled radiolabeled tracers from the lung is
in 1%. impaired in bronchiectasis this is non-specific and seen in other
airways disease so cannot be considered diagnostic of bronchi-
Section 4 ectasis. (2-)
How should the diagnosis of bronchiectasis be determined?
Imaging Recommendations - Imaging
There are no randomised controlled trials comparing different ➢➢ Perform baseline chest X-ray in patients with suspected
imaging techniques in establishing a diagnosis of bronchiectasis bronchiectasis. (D)
but there are several cohort studies of low to moderate quality ➢➢ Perform a thin section CT to confirm a diagnosis of bronchi-
as well as case series. Compared with HRCT sensitivity of ectasis when clinically suspected. (C)
CXR was 87.8% and specificity 74.4%.5 Compared with bron- ➢➢ Perform baseline imaging during clinically stable disease as
chography, thin section CT performed with 10 mm interspaces this is optimal for diagnostic and serial comparison purposes.
demonstrated a high accuracy in diagnosing bronchiectasis with (D)
false positive and negative rates for CT were 1% and 2% respec-
tively.6 Volumetric CT has improved sensitivity and interob- Good practice points
server agreement compared with incremental/interspaced thin CT imaging protocol
slice CT.7 8 Bronchiectasis was identified more commonly in ✓✓ The most appropriate imaging protocol will vary according
helical than incremental thin slice images. Interobserver agree- to scanner technology and patient factors.
ment was significantly better on a per segment basis with helical ✓✓ When using volumetric CT, dose reduction techniques
CT (kappa 0.87) than incremental (kappa 0.71), but radiation including adaptive mA and kV and iterative reconstruction
dose of helical CT was 3.4 times higher. Multidetector CT should be utilised where available.
(MDCT) yielded higher sensitivity and specificity for the detec- ✓✓ Typical CT imaging parameters for the diagnosis of bronchi-
tion of bronchiectasis. Using MDCT as the reference standard ectasis are:
and analysing data on a per lobe basis the sensitivity, specificity, ºº Slice thickness:≤1 mm
positive and negative predictive values for incremental HRCT ºº Reconstruction algorithm: – high spatial frequency
were 71%, 93%, 88% and 81% respectively. Interobserver ºº kVp: 100–140
agreement was also higher for MDCT.9 ºº mAs (or effective mAs): 100–200
While the dose using volumetric CT using the same param- ºº Gantry rotation time:<0.5 s
eters is increased in comparison to incremental/interspaced
images modifications of technique enable improved diag- CT features of bronchiectasis
nostic accuracy with similar radiation dose.7–9 Jung et al ✓✓ Bronchiectasis is defined by bronchial dilatation as suggested
concluded that low dose CT at 40mAs provides more diag- by one or more of the following:
nostic information in the evaluation of bronchiectasis than ºº Bronchoarterial ratio >1(internal airway lumen vs adja-
incremental HRCT.10 cent pulmonary artery)
While clearance of inhaled radiolabeled tracers from the lung ºº Lack of tapering
is impaired in bronchiectasis this is non-specific and seen in other ºº Airway visibility within 1 cm of costal pleural surface or
airways disease so cannot be considered diagnostic of bronchi- touching mediastinal pleura.
ectasis. Chronic bronchitis, bronchiectasis and asthma were all ✓✓ The following indirect signs are commonly associated with
associated with slower clearance of inhaled radiolabeled tracers bronchiectasis:
than healthy non-smokers (P<0.005) with overlap between ºº Bronchial wall thickening
these disease groups.11 ºº Mucus impaction
Currie et al assessed radio-aerosol tracheobronchial clear- ºº Mosaic perfusion/air trapping on expiratory CT
ance in first 6 hours in bronchiectasis (12 patients), COPD with
sputum (7), COPD without sputum (8) and healthy controls.12 General
In bronchiectasis tracheobronchial clearance of inhaled radiola- ✓✓ CT scanning can also aid in identifying an aetiology of bron-
beled tracers was significantly lower than controls but similar to chiectasis for example, ABPA, NTM, primary ciliary dyski-
COPD patients. nesia, alpha one antitrypsin deficiency, Williams Campbell
Ashford et al showed that ventilation scintigraphy with 99mTc syndrome and a foreign body.
DTPA in 20 patients with suspected bronchiectasis had low
sensitivity for bronchiectasis (56%) using bronchography as the
reference standard.13 Section 5
In whom should the diagnosis of bronchiectasis be
Evidence statements suspected?
Chest radiography (CXR) has limited sensitivity and specificity The most common symptom in bronchiectasis is cough particu-
in diagnosing bronchiectasis particularly in mild disease (2+). larly with sputum production.14 15
Compared with bronchography thin section CT performed with Appendices 5 and 6 show the causes identified from inter-
10 mm interspaces has a high accuracy in diagnosing bronchiec- national studies. Often no cause is found despite aetiological
tasis. (2+) testing. Past infection (such as measles, whooping cough, pneu-
Volumetric CT has improved sensitivity and interobserver monia or tuberculosis) and is a possible cause of bronchiec-
agreement compared with incremental/interspaced thin slice tasis, particularly if persistent symptoms develop soon after the
CT. (2+) infection.
12 Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463
BTS Guideline
Specific disease groups with associated bronchiectasis may pre-date the diagnosis of even seropositive RA. Significantly
COPD more erosive changes were observed on hand and foot radiology
A meta-analysis of 6 observational studies found that the prev- in 53 patients with bronchiectasis and RA versus 50 patients with
alence of bronchiectasis was 54.3% (range 25.6%–69%), more RA alone, and both rheumatoid factor (RF) and anti-cyclic citrul-
common in males (OR 1.62, 95% CI 1.15 to 2.28) and with a linated peptide (anti-CCP) antibodies were higher in those with
greater smoking history (weighted mean difference 4.63 pack bronchiectasis.39 In that study, bronchiectasis preceded the onset
years, 95% CI 1.61 to 7.65 pack years). Other features that of RA in 58%.39
distinguished patients with COPD and bronchiectasis from A large study on patients hospitalised with RA established
COPD alone included greater daily sputum production, higher the frequency of appropriate symptoms first and then inves-
exacerbation frequency, worse lung function, higher levels of tigated with CT scan. Out of 453 patients questioned, 13
inflammatory biomarkers, increased colonisation by potential had symptoms suspicious for bronchiectasis and 9 of the
pathogenic micro-organism (PPM) and increased rate of Pseu- 10 patients scanned had confirmed bronchiectasis, giving a
domonas aeruginosa (P. aeruginosa) colonisation.16 A systematic prevalence of 2.9% of symptomatic bronchiectasis in this
review and meta-analysis of 14 observational studies in COPD population.40
patients found that the presence of bronchiectasis was associated
with worse airflow obstruction, isolation of PPM, increased risk
of exacerbation and of mortality.17 Other connective tissue diseases
Bronchiectasis has been noted in other connective tissue diseases
including primary Sjogren’s syndrome, Marfan’s syndrome,
Alpha-1 antitrypsin deficiency (A1AT) systemic sclerosis, systemic lupus erythematosus, and ankylosing
A retrospective cohort study between 1995 and 2002 of 74 spondylitis.
patients with PiZZ deficiency (mean age 50.6, SD 9.2 years) A study of a 507 patient cohort with primary Sjogren’s
found radiological evidence of bronchiectasis in 94.5%.18 syndrome (PSS) identified 120 patients with suspected pulmo-
Another retrospective cohort study of 26 Irish patients with nary disease, and found bronchiectasis on CT scan in 50
A1AT deficiency found that 14 had bronchiectasis, all of whom patients.41 Retrospective studies confirm the association.42–44
had PiZZ phenotype.19 A retrospective review of 79 patients with Marfan’s who
underwent HRCT imaging found evidence of bronchiectasis
in 28%.45 Airway dilatation was described as not severe, often
Asthma confined to one lobe and was said to localise with anatomical
A careful cross-sectional analysis of 85 patients in secondary care abnormalities such as pectus excavatum, although fibrosis due
with bronchiectasis found asthma in 27% of the clinic popula- to previous tuberculosis was noted in some patients.45 Studies
tion while prevalence of asthma in the general population was in ankylosing spondylitis have found incidence of bronchiec-
7%.20 A large study of patients with difficult asthma found bron- tasis to range from 7.2% to 51.2%.46–51 In 7 of 34 patients
chiectasis on CT scan in 40% of selected patients; the criteria with systemic lupus erythematosus (SLE) who prospectively
for scanning were not stated but the scanned patients were underwent HRCT imaging, bronchiectasis was observed.52
older, with a longer duration of disease, on more corticosteroid A small study of systemic sclerosis found a high rate of bron-
treatment and with poorer lung function and more neutrophilic chiectasis on CT in 13 (59.1%) of 22 patients.53 In a study
airway inflammation on sputum cytology than those who were of scleroderma and pulmonary hypertension, bronchiectasis
not scanned.21 In a case-control study matching patients with independent of interstitial lung disease (ILD) was found on
steroid-dependent asthma to those managed without regular CT scan in 6 of 44 patients with restrictive lung function or
oral corticosteroids, it was noted that bronchiectasis was much crackles.54
more common in the former group and the overall prevalence
of otherwise unexplained bronchiectasis was 12% across both Inflammatory Bowel Disease
groups, rising to 20% in the steroid-dependent group.22 There is a recognised association between bronchiectasis and
inflammatory bowel disease (IBD). A prospective study of 95
patients with IBD (83 ulcerative colitis (UC) and 12 Crohn’s
Rhinosinusitis disease (CD)) who underwent HRCT scans found evidence of
Rhinosinusitis is common in bronchiectasis patients,23 but bronchiectasis in 9, all of whom had UC and no reported respi-
only one study appears to have assessed the prevalence of ratory symptoms.55 A cohort study of 30 UC and 9 CD patients
bronchiectasis in chronic sinusitis, finding it in 3 out of 60 undergoing CT scans found bronchiectasis in two patients.56 In
patients (5%).24 36 consecutive IBD patients (23 UC, 13 CD) studied for pulmo-
nary disease, bronchiectasis was found on CT in three patients.
Chronic systemic infection 44% of the total study population had respiratory symptoms,
Chronic infection such as HIV or HTLV-1 appears to increase but sputum production was described in only two patients-
the risk of bronchiectasis.25 26 27 28 the relationship between symptoms and CT findings was not
described.57 A literature review found bronchiectasis in 44 out
of 155 patients with inflammatory bowel disease.58
Rheumatoid arthritis A retrospective case note review of 10 patients with IBD
Clinical studies of patients with rheumatoid arthritis (RA) have (5 UC, 5 CD) and bronchiectasis found that eight had developed
found varying rates of bronchiectasis on CT scan ranging from respiratory symptoms only following surgery for their IBD.59
4% to 58%.29–38 These patients had had IBD for a median of 15 (9-35) years and
The diagnosis of bronchiectasis may occur in early or estab- for those developing pulmonary symptoms following surgery,
lished RA, and presentation and diagnosis with bronchiectasis the time from surgery to symptoms ranged from 2 weeks to 30
Table 4 Variables involved in calculating the severity score in the Bronchiectasis severity index
Factor and points for scoring system
Age (years) <50 (0 points) 50–69 (2 points) 70–79 >80 (6 points)
(4 points)
BMI (Kg/m2) <18.5 (2 points) 18.5–25 (0 points) 26–30 (0 >30 (0 points)
points)
FEV1% predicted >80 (0 points) 50–80 (1 point) 30–49 <30 (3 points)
(2 points)
Hospital admission within last 2 years No (0 points) Yes (5 points)
Number of exacerbations in previous 12 months 0 (0 points) 1–2 (0 points) ≥3 (2 points)
MRC breathlessness score 1–3 (0 points) 4 (2 points) 5 (3 points)
P. aeruginosa colonisation No (0 points) Yes (3 points)
Colonisation with other organisms No (0 points) Yes (1 point)
Radiological severity <3 lobes affected (0 points) ≥3 lobes or cystic bronchiectasis in any lobe (1 point)
0-4 Points=mild disease; 5–8=moderate disease; 9 and over=severe disease.
important limitation) and it is not known whether a change in patients who require management of continence issues and
score reflects a change in prognosis. musculoskeletal dysfunction.126 In this way, a physiotherapist
The BSI combines age, body mass index, FEV1, previous aims to optimise a patient’s physical function.
hospitalisation, exacerbation frequency, colonisation status
and radiological appearances. The score was designed to
predict future exacerbations and hospitalisations, health- Which patients should be taught airway clearance techniques?
status, and death over 4 years. Patients with NTM were A single randomised crossover trial has been published which
excluded. Data were provided which examine how the score assesses the efficacy of regular respiratory physiotherapy versus
performed in annual prediction of events, a more relevant no respiratory physiotherapy in participants with bronchiectasis
clinical scenario than provided for FACED, and the team have and chronic sputum expectoration.124 Twenty stable outpatients
developed a useful online calculator (available at www.bron who did not practice regular respiratory physiotherapy were
chiectasisseverity.com). A score of 0–4 (mild) is associated with included. The intervention comprised of twice daily 20–30 min
0%–2.8% mortality and 0%–3.4% hospitalisation rate over sessions of respiratory physiotherapy using an oscillating posi-
1 year, and 0%–5.3% mortality and 0%–9.2% hospitalisation tive expiratory pressure device (Acapella Choice) over a 3 month
rate over 4 years. period. There was a significant improvement in all domains
Outcomes in moderate bronchiectasis (score 5–8) were and the total Leicester Cough Questionnaire (LCQ) score with
0.8%–4.8% mortality and 1.0%–7.2% hospitalisation rate at regular respiratory physiotherapy (median (IQR) (1.3 (−0.17–
1 year and 4%–11.3% mortality and 9.9%–19.4% hospital- 3.25) units; P=0.002). It should be noted that the MCID for
isation rate at 4 years. A score over 9 (severe bronchiectasis) LCQ is 1.3 units.127 Sputum volume measured over 24 hours
was associated with 1 year 7.6%–10.5% mortality, and 16.7%– increased significantly with regular respiratory physiotherapy (2
52.6% hospitalisation rate and a 4 year 9.9%–29.2% mortality (0–6) mL; P=0.02) as did exercise capacity as measured by the
and 41.2%–80.4% hospitalisation rates. Understanding the
incremental shuttle walk test (ISWT) (40 (15-80) m; P=0.001).
factors associated with future morbidity and mortality in bron-
There was also a significant improvement in quality of life (QoL)
chiectasis provides a rationale, discussed further elsewhere,
with a significant improvement in the St George’s Respiratory
for which variables should be assessed and monitored in
Questionnaire (SGRQ) total score (7.77 (−0.99–14.5) unit
bronchiectasis.
improvement; P=0.004). No sham treatment was provided
in the no respiratory physiotherapy arm and so there is some
Good practice point
potential for a placebo effect. However, this study does provide
✓✓ Consider using the bronchiectasis severity index which may
low-quality evidence that regular twice daily respiratory physio-
help guide management.
therapy is effective in stable patients.
Section 9
Stable state treatment
Airway clearance techniques Table 5 Variables involved in calculating severity in the FACED score
Respiratory physiotherapy aims to mobilise secretions and Factor and points for scoring system
aid effective expectoration, improving airway clearance and FEV1% predicted <50 (2 points) ≥50 (0 points)
providing some control of cough.124 The other aims of respi-
Age (years) ≤70 (0 points) >70 (2 points)
ratory physiotherapy include improving efficiency of ventila-
tion, maintaining or improving exercise tolerance, improving Colonisation by P. aeruginosa No (0 points) Yes (1 point)
knowledge and understanding, and reducing breathlessness and Radiological extension of 1–2 lobes (0 points) >2 lobes (1 point)
(thoracic) pain.125 The physiotherapist can discuss step up and bronchiectasis
step down airways clearance techniques in managing exacer- Modified MRC dyspnoea scale 1–2 (0 points) III-IV (1 point)
bations. In addition, the respiratory physiotherapist can assist 0–2 Points=mild disease; 3–4=moderate disease; 5–7=severe disease.
Evidence statement
Evidence statements for airway clearance techniques Oscillating positive expiratory pressure (Acapella) (plus postural
The active cycle of breathing techniques is as effective as oscil- drainage) is effective and safe to use during an acute exacerba-
lating positive expiratory pressure (Flutter and Acapella) at tion. (1-)
clearing sputum. (1-)
The active cycle of breathing techniques plus postural drainage
enhances the quantity of sputum expectorated compared with Good practice points
the active cycle of breathing techniques in the sitting position ✓✓ Manual techniques may be offered to enhance sputum
or oscillating positive expiratory pressure (Flutter) in the sitting clearance when the patient is fatigued or undergoing an
position. (1-) exacerbation.
The active cycle of breathing techniques (plus postural ✓✓ Consider intermittent positive pressure breathing or non-in-
drainage and vibration) is more effective at clearing sputum than vasive ventilation during an acute exacerbation to offload the
the test of incremental respiratory endurance. (1-) work of breathing so fatigued and/or breathless patients can
Oscillating positive expiratory pressure (Acapella) is more tolerate a longer treatment session and can adopt postural
effective at clearing sputum than a threshold inspiratory muscle drainage positions.
trainer. (1-)
Oscillating positive expiratory pressure (Acapella) improves Research recommendations
QoL, sputum volume expectorated and exercise capacity Randomised controlled trials using clinically important outcome
compared with no airway clearance technique over a 3 month measures are required to assess the effectiveness of airway clear-
period. (1-) ance techniques in varying severities of bronchiectasis.
High frequency chest wall oscillation improves breathlessness, Randomised controlled trials are required to evaluate the
quality of life, sputum volume and lung function. (1-) effects of airway clearance techniques in patients who are under-
going an exacerbation.
Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463 23
BTS Guideline
How often should patients carry out airway clearance expectorants (humidification, normal/isotonic saline (0.9%
techniques? How long should an airway clearance session saline) (IS), hypertonic saline (3% saline and above) (HS)153–158
last? and mannitol159 160 and there is a small amount of evidence in
Duration mucoregulators (erdosteine)161 and bromhexine.162
Most clinicians would advocate the use of an airway clearance
technique for a period specific to the individual. Commonly, not Humidification
more than 30 min is recommended. The aim is to perform the A small study (n=7) showed that 30 min of cold water, jet
airway clearance technique until two clear huffs or coughs are nebulising humidification via a facemask before respiratory
completed. However, this is not always practical in those who physiotherapy (postural drainage and the forced expiration
are extremely productive. It is important that a balance is found technique) significantly increased sputum yield and radio
between making sure that the treatment is long enough to maxi- aerosol clearance compared with respiratory physiotherapy
mise airway clearance, but not so long that the patient becomes alone.154 A further study (n=10) using warm air humidifica-
fatigued. tion for 3 hours a day also showed a significant increase in
radiolabelled clearance in the treatment group compared with
Frequency the control group.163
The frequency of the airway clearance technique should be
specific to the needs of the individual patient and probably
increased during an infective exacerbation. There is no evidence
Saline
A small single study (n=8) found that the use of nebulised IS
to support a particular frequency with recommendations of once
immediately before respiratory physiotherapy (postural drainage
or twice daily treatment commonly given.
and the forced expiration technique) yielded significantly more
sputum than physiotherapy alone.153
Good practice points A four way single intervention crossover study looking at
✓✓ The frequency and duration of the airway clearance tech- ACBT alone, ACBT and terbutaline, ACBT and isotonic saline
nique should be tailored to the individual and may alter (IS) and ACBT and hypertonic saline (HS), suggested that HS
during periods of exacerbation. gave an additional improvement to QoL, FEV1, sputum weight,
✓✓ Advise individuals to perform their airway clearance tech- ease of expectoration and viscosity in addition to the benefit
nique for a minimum of 10 minutes (up to a maximum of 30 shown by IS over that of terbutaline or ACBT alone.158
minutes). After this time they should continue until two clear A 4 week crossover study in 32 patients with bronchiectasis
huffs or coughs are completed, or until the patient is starting compared 7% HS to a placebo (IS). FEV1 improved in the HS
to become fatigued. group compared with the IS group by 15.1 (1.8)% (P<0.01);
FVC by 11.2 (0.7)% (P<0.01), QoL as measured by SGRQ
How soon should the patient be reviewed after the initial showed an improvement of 6 units (P<0.05) in the HS group.155
assessment? Moreover sputum viscosity (subjective pourability), ease of
Initial assessment may take up to an hour, with education clearance (as measured by a visual analogue scale) and health-
and instruction of an appropriate airway clearance technique care utilisation also all improved in the HS group compared
included. A review of the individual’s ability to effectively carry with IS.
out this technique should be undertaken within 3 months of this A long term study (12 months) of 40 participants was designed
initial appointment.126 to investigate the impact of HS compared with IS when used
with ACBT, demonstrated that both IS and HS saline had a
positive impact on all domains of the SGRQ and the LCQ after
Good practice points three, six and 12 months, and on FEV1, with an improvement
✓✓ Individuals that have been assessed and taught an airway
in the IS group of (mean) 90 mL (11 to 169); P=0.04 compared
clearance technique should be reviewed by a respiratory
with baseline.157
physiotherapist within 3 months of their initial assessment.
In summary this evidence suggests that HS may improve QoL
✓✓ Individuals with bronchiectasis who are followed up in
outcomes and sputum clearance in individuals with bronchiec-
secondary care should be assessed by a respiratory physi-
tasis, however it is unclear if this benefit is over and above that
otherapist as part of their annual clinical review to ensure
of IS.
their airway clearance regimen is optimised.
✓✓ All individuals with a deterioration in their condition
(increased frequency of exacerbations and/or worsening of Mannitol
symptoms) should have their airway clearance technique Many studies have suggested an in vitro benefit of mannitol164
reviewed by a respiratory physiotherapist (See figure 1 – and have shown it to be tolerated in inhaled devices by indi-
management of the deteriorating patient). viduals with bronchiectasis in feasibility studies.165 In a phase
three study of 343 subjects with bronchiectasis,159 subjects were
Mucoactives in bronchiectasis randomised into either placebo (40 mg mannitol) versus treatment
Mucoactive medications describe medications which may have a dose mannitol (340 mg) over a 12 week intervention period. An
direct impact on the clearance of mucus from airways. These can improvement was seen in SGRQ in the mannitol group, however
be defined by their different methods of action including expec- this was not a clinically significant change. A subgroup of partic-
torants (aid and/or induce cough), mucolytics (thin mucus), ipants (n=123) who continued to a further 52 weeks open label
mucokinetics (facilitate cough transportability), and mucoreg- study continuing on mannitol had a reduction in sputum plug-
ulators (suppress mechanisms underlying chronic mucus hyper ging on CT scan. In a large phase 3 RCT in 461 patients with
secretion, such as glucocorticosteroids). Bronchiectasis research bronchiectasis over 12 months,160 randomised patients received
has mainly focused on mucolytics (DNase),151 152 mucokinetics/ either placebo (low dose mannitol) or mannitol (400 mg) over
24 Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463
BTS Guideline
12 months. No differences were seen in the primary end point Evidence statements
of exacerbation frequency between the two groups at these time Recombinant human DNase increases exacerbation frequency in
points. However, this study did show a prolongation in time to bronchiectasis. (1+)
first exacerbation and a small improvement in quality of life in Isotonic and hypertonic saline can improve cough related
the mannitol group. quality of life QoL and health related quality of life (HQoL)
In view of the potential for bronchoconstriction, a challenge in patients with bronchiectasis in addition to airway clear-
test with hyperosmolar agents is suggested. All included studies ance. (1-)
performed a challenge test to assess for bronchoconstriction Mannitol did not improve exacerbation frequency but was
and/or bronchial hyper-reactivity prior to use of the device/ shown to increase the time to first exacerbation, demonstrated
medication.155–160 Those individuals who reported chest tight- a small improvement in QoL and may reduce sputum plugging.
ness, wheeze, and difficulty in breathing or had a 10% or 15% (1+)
reduction in spirometry were withdrawn from the studies. All The use of humidification prior to airway clearance improves
the studies suggested that such events were minimal thereby sputum yield and radiolabeled clearance, when used in short
showing good tolerance of hypertonic saline and mannitol. The term interventions (>1 month). (3)
studies varied on the use of a pre dose bronchodilator. However Oral mucolytics can improve sputum expectoration. (1-)
clinical practice suggests that pre-treatment with a bronchodi-
lator may be necessary for those with the potential for bronchial Recommendations
hyper-reactivity (eg, a diagnosis of asthma, or defined broncho- ➢➢ Do not routinely use recombinant human DNase in adults
dilator reversibility). with bronchiectasis. (A)
➢➢ Consider the use of humidification with sterile water or
normal saline to facilitate airway clearance. (D)
Mucolytics
Recombinant human DNase (DNase, dornase alpha, Pulmo- Good practice points
zyme) breaks down the DNA released at the site of infection ✓✓ Consider a trial of mucoactive treatment in patients with
by the neutrophils. DNA causes the sputum to become thick bronchiectasis who have difficulty in sputum expectoration.
and tenacious and therefore inhaled DNase makes the sputum ✓✓ Perform an airway reactivity challenge test when inhaled
less viscid and therefore easier to expectorate. A multi-centre mucoactive treatment is first administered.
study in 349 patients with idiopathic bronchiectasis randomised ✓✓ Consider pre-treatment with a bronchodilator prior to
patients to use either 2.5 mg DNase versus a placebo.152 There inhaled or nebulised mucoactive treatments especially in
was a significant increase in the rate of both protocol-defined individuals where bronchoconstriction is likely (patients
exacerbations (0.66 rate of exacerbations per patient per 166 with asthma or bronchial hyper-reactivity and those with
days compared with 0.56 rate for those in placebo group, relative severe airflow obstruction FEV1 <1 litre).
risk=1.17) as well as an increase in non-protocol defined exacer- ✓✓ If carbocysteine is prescribed, a 6 month trial should be given
bations (relative risk 2.01) within the DNase group. DNase had and continued if there is ongoing clinical benefit.
a small but negative effect on FEV1 (−3.6% in DNase v 1.7% in See figures 3 and 4.
control, P=0.05) See appendix 2: Challenge test details
There have been very few trials reviewing the use of oral
mucolytics in bronchiectasis. One study (n=88) reviewed the Research recommendation
addition of bromhexine hydrochloride to an antibiotic during Randomised controlled trials are needed to assess the long term
an acute infective exacerbation compared with a placebo.162 impact of muco-active therapies.
It is thought this medication may influence sputum clearance
by increasing the production of serous mucus thereby making
the sputum thinner and less viscous. Results suggest that this What is the evidence for long term anti-inflammatory
medication was effective, as the percentage change in sputum therapies in bronchiectasis?
production was greater in the bromhexine group at 7, 10 and Airway inflammation is dominated by neutrophils although
16 days (mean difference (MD) −21.5 mL, 95% CI −38.9 to there is evidence to implicate multiple other inflammatory cells
−4.1 at day 16). Moreover the difficulty in expectoration was and pathways in the pathophysiology of bronchiectasis.167 168
also improved in the bromhexine group at day 10 (MD −0.53,
95% CI −0.81 to −0.25) however it had no impact on FEV1. Inhaled corticosteroids (ICS)
Bromhexine hydrochloride is not widely available in the UK and In bronchiectasis, a systematic review conducted in 2009 identi-
is not listed in the BNF. fied six single centre randomised controlled trials.169 Two studies
Erdosteine is another mucolytic which is thought to modu- were crossover studies170 171 while the other four were parallel
late mucus production through the scavenging activity of free group studies.172–175 All were double blind placebo controlled
radicals. A study in 2007 compared the use of erdosteine and studies with the exception of Martinez et al 2006 which was
respiratory physiotherapy to respiratory physiotherapy alone open label.172 Studies used multiple difference steroid prepara-
over a 15 day period in a bronchiectasis population (n=30).161 tions and doses (beclomethasone 800 µg/day, 1500 µg, flutica-
This study was small and of poor methodological quality due sone 500 µg/day and 1000 µg/day). Study duration ranged from
to limited control of bias. Small changes were seen in some 4 to 6 weeks to 6 months. Two studies reported reductions in
subjective sputum characteristics and FEV1 in the erdosteine sputum volume with ICS treatment.170 172 A small improvement
group. in lung function was suggested by the meta-analysis (90 mL for
In the UK from National Audits 2010 and 2011, Carbocys- FEV1 and FVC) in studies of ≤6 months but this was not statis-
teine was commonly prescribed (27%–30%).166 There are no tically significant if the study that was not placebo controlled
randomised controlled trials to demonstrate benefit. was removed.169 No reduction in exacerbations was identified.
Offer active cycle of breathing If ACBT is not effective or the patients If airway clearance is not effective then
techniques (ACBT) to individuals demonstrates poor adherence, nebulised Isotonic (0.9% saline) or
with bronchiectasis. oscillating Positive Expiratory Pressures Hypertonic Saline (3% saline and above)
+ Forced Expiration Technique should be evaluated for its effectiveness
Consider gravity assisted pre-airway clearance (especially in
should be considered.
positioning (where not patients with viscous secretions or
contraindicated) to enhance the there is evidence of sputum plugging)
effectiveness of an airway
clearance technique. If
contraindicated then modified Individuals should be advised to
postural drainage should be used. complete Airway Clearance in the
following order, if prescribed:
– Bronchodilator
In longer term studies (>6 months) no significant improvement Phosphodiesterase four inhibitors (PDE4 inhibitors)
in lung function or exacerbations were identified.169 The BTS There are no randomised trials of PDE4 inhibitors in bronchiec-
guideline development group identified no new randomised tasis. In addition, no observational data were identified.
controlled trials since 2009.
Clinically important adverse events associated with inhaled
corticosteroids have been identified. Holme et al identified a high Methylxanthines
frequency of adrenal suppression associated with ICS treatment No randomised controlled trials were identified in bron-
in bronchiectasis.176 A statistically significant increase in adverse chiectasis for these drugs.179 No observational data were
effects was reported for high dose ICS in the trial of Martinez et al identified.
(P=0.04).172 A trial of high dose budesonide vs budesonide with
formoterol identified a numerical increase in the frequency of local
side effects with high dose ICS (pharyngeal irritation, dysphonia Indomethacin
and gingivitis) and a single case of pneumonia which is a recognised A single trial of 25 adults with chronic lung diseases that included
adverse effect of inhaled corticosteroid treatment in COPD.177 patients with bronchiectasis was identified. This study showed
a significant reduction in sputum production over 14 days in
Oral corticosteroids patients that received inhaled indomethacin compared with
No randomised controlled trials of oral corticosteroids either placebo (difference −75 g/day 95% CI −134.6 to −15.4).180
when stable or during exacerbations could be identified.178 No There were also significant improvements in dyspnoea. No
observational data were identified. further large trials have been performed.
Increase airway clearance frequency. Commence the use of mPD or PD if Individuals with ongoing difficulty with airway clearance may
E.g.: from twice daily to three/four tolerated. benefit from the addition of other techniques. It is recommended
times daily. that these should be commenced and evaluated in the following
For individuals with radiological order (unless contraindicated)
changes, PD or mPD should be targeted
1. Enhanced humidification / hydration of airways if
appropriately.
secretions viscous (isotonic (0.9% saline) or hypertonic
saline (3% saline and above)/humidification/increased fluid
intake)
2. Manual Techniques
3. Positive pressure devices including Intermittent Positive
Pressure Breathing (IPPB) or Non Invasive Ventilation
PD=postural drainage; mPD= modified postural drainage (NIV) to be used during Airway Clearance
Leukotriene receptor antagonists A small randomised trial of oral neutrophil elastase inhibitors
No randomised trials or observational studies of leukotriene in bronchiectasis showed improved FEV1 but no other benefits.
receptor antagonists in bronchiectasis have been performed.181 (1-)
A small trial of CXCR2 antagonists showed reduced sputum
neutrophil counts but no clinical benefits. (1-)
Neutrophil elastase inhibitors
A small randomised trial of statins in bronchiectasis showed
Neutrophil elastase is a proteolytic enzyme released by neutro-
improved cough, but an increase in adverse events. (1-)
phils which may have a role in disease progression.182 A single
A small randomised trial of statins in bronchiectasis chron-
randomised controlled trial of 38 patients treated with a neutro-
ically infected with P. aeruginosa showed improved health
phil elastase inhibitor for 4 weeks compared with placebo
related quality of life. (1-)
(n=16) was identified. The study found no difference in sputum
neutrophils but an improvement of 100 mL in the FEV1 in the
NE inhibitor group (P=0.006).183 No larger trials have yet been Recommendations
performed. ➢➢ Do not routinely offer inhaled corticosteroids to patients
with bronchiectasis without other indications (such as
CXCR2 inhibitors ABPA, chronic asthma, COPD and inflammatory bowel
A double blind randomised placebo-controlled trial of the CXCR2 disease). (B)
antagonist AZD5069 in bronchiectasis for 28 days recruited 52 ➢➢ Do not offer long-term oral corticosteroids for patients
patients with a primary outcome of sputum neutrophil counts. with bronchiectasis without other indications (such as
This study showed a significant reduction in absolute neutrophil ABPA, chronic asthma, COPD, inflammatory bowel
counts (69% vs placebo, P=0.004). There was no significant disease). (D)
difference in exacerbations or other clinical outcomes. Some ➢➢ Do not routinely offer PDE4 inhibitors, methylxanthines
sputum inflammatory markers e.g IL-6, GRO-α, IL-1β and IL-8 or leukotriene receptor antagonists for bronchiectasis treat-
increased with AZD5069 vs placebo. Four patients discontinued ment. (D)
therapy in the active group vs 0 in the placebo group.184 ➢➢ Do not routinely offer CXCR2 antagonists, neutrophil
elastase inhibitors or statins for bronchiectasis treatment. (B)
Statins
Statins have multiple anti-inflammatory and immunodulatory Good practice point
effects in addition to their effects on cholesterol. A randomised ✓✓ Inhaled corticosteroids have an established role in the manage-
placebo controlled trial has been performed in bronchiectasis. ment of asthma and a proportion of patients with COPD
60 patients were treated with atorvastatin 80 mg daily for 6 which are common co-morbid conditions in bronchiectasis.
months (n=30) vs. placebo (n=30).185 The primary endpoint
was improvement in cough assessed by the Leicester Cough
Questionnaire. The change from baseline to 6 months in
Research recommendation
Randomised controlled trials are needed to assess the long term
LCQ score differed between groups, with a mean change of
impact of anti-inflammatory therapies.
1.5 units in patients allocated atorvastatin versus –0.7 units in
those assigned placebo (mean difference 2·2, 95% CI 0·5–3·9;
P=0·01). 12 (40%) of 30 patients in the atorvastatin group What treatments improve outcomes for patients with stable
improved by 1.3 units or more on the LCQ compared with bronchiectasis?
five (17%) of 30 in the placebo group (difference 23%, 95% CI Long term antibiotic treatment (>=3 months)
1–45; P=0·04). Ten (33%) patients assigned atorvastatin had Oral antibiotics
an adverse event versus three (10%) allocated placebo (differ- Several randomised controlled studies have been performed to
ence 23%, 95% CI 3–43; P=0·02).185 No larger trials have ascertain the effect of long term antibiotics in bronchiectasis.
been performed. Some of the earliest were performed in the 1950s and so the
A randomised placebo cross-over trial investigated atorvas- diagnostic techniques defining the patient population (bron-
tatin 80 mg daily for 3 months in patients chronically infected chiectasis and aetiology), outcome measures, statistical analysis
with P. aeruginosa. Statin therapy did not improve the primary and trial conduct are suboptimal by contemporary standards.
endpoint for improved cough assessed by the Leicester Cough The MRC study published in 1957 involved 122 bronchiectasis
Questionnaire. There were however significant improvements in patients from seven centres randomised to receive penicillin
the St. George’s Respiratory Questionnaire (5.6 Unit improve- 500 mg four times a day or oxytetracycline 500 mg four times a
ment) and a reduction in serum CXCL8, TNFα and ICAM-1 in day or identical placebo two capsules four times a day, for 2 days
the statin treated group.186 per week for 1 year.187 No power calculation or formal statis-
tical analysis was performed and no qualitative or quantitative
sputum microbiology was performed. Oxytetracycline appeared
Evidence statements most efficacious with least exacerbations requiring rescue antibi-
Inhaled corticosteroids may reduce sputum volume in bronchi- otics, a 50% reduction in sputum purulence, markedly less days
ectasis but are associated with adverse events including local and confined to bed and less days off work. Treatment with penicillin
systemic effects. (1+) appeared to be associated with a marginal treatment response
There was insufficient evidence to evaluate the role of oral compared with placebo. A study by Cherniack et al published
corticosteroids, PDE4 inhibitors, methylxanthines or leukot- in 1959 involved 67 patients (45 with bronchiectasis) from a
riene receptor antagonists in bronchiectasis. (4) single centre.188 Patients were randomised to receive tetracycline
A small trial of inhaled indomethacin which included some (2 g/day), Penicillin G (1,600,000 units/day) Oleandomycin-Pen-
patients with bronchiectasis showed reduced sputum volume icillin (2 g/day) or identical placebo. In a subgroup analysis
and improved dyspnoea. (1-) involving only patients with proven bronchiectasis, there were
Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463 27
BTS Guideline
no statistically significant differences between the treatment Altenburg that it is lost (in terms of exacerbations).191 Wong
groups but this may reflect a lack of power.188 A further study in found treatment effects significantly greater in patients with
38 bronchiectasis patients looked at the use of daily oral amoxi- higher SGRQ scores.190 There is some evidence favouring azith-
cillin 3 g bd over 32 weeks. In this study CTs were not performed romycin. The Guang Ying et al meta analysis showed that on
and no reduction in exacerbations was demonstrated, but some subgroup analysis azithromycin demonstrated lower exacerba-
improvement in sputum volume, diary card symptom improve- tion frequency whereas erythromycin did not.195 In addition,
ment and less time away from work.189 These studies suggest that the benefit of erythromycin compared with placebo was more
tetracycline based regimens may reduce exacerbation frequency, delayed in the erythromycin study compared with the other two
duration of illness and improve symptoms in patients with bron- azithromycin studies. The latter observation may however be
chiectasis, with penicillin based regimens being less effective. accounted for by the higher proportion of P. aeruginosa patients
Recent longer term antibiotic trials have only enrolled patients in this study.
with bronchiectasis confirmed by high resolution CT scans. The A further analysis by 16S RNA gene sequencing of paired
primary clinical endpoints have concentrated on exacerbation sputum samples, baseline and end of treatment, from the BLESS
burden with either time to next exacerbation or exacerbation trial showed a reduced abundance of H. influenzae, and an
frequency. There have been three recent, high quality (although increased relative abundance of P. aeruginosa, in patients treated
small studies and heterogeneous design) RCTs performed with erythromycin without P. aeruginosa at the start of the
comparing a macrolide antibiotic to placebo given over 6–12 trial.192 This was not shown by routine bacteriology, but raises a
months. concern which requires further investigation.197
Non- P. aeruginosa colonised patients Does long term bronchodilator treatment improve outcomes
e. Use azithromycin or erythromycin for patient with bron- for patients with bronchiectasis?
chiectasis. (A) Patients with bronchiectasis frequently have airflow obstruction
f. Consider inhaled gentamicin as a second line alternative and more than 60% of bronchiectasis patients have daily symp-
to azithromycin or erythromycin. (B) toms of breathlessness.120 There is limited supporting evidence
g. Consider doxycycline as an alternative in patients intol- for the use of bronchodilators, although both beta-2-agonists
erant of macrolides or in whom they are ineffective. (C) and anticholinergic bronchodilators are commonly used in clin-
ical practice.166
Good practice points
✓✓ Antimicrobial stewardship is important Long acting Beta-2-agonists
✓✓ Prior to starting long term macrolides, for safety reasons: 1) A systematic review published in 2014 identified only one
ensure no active NTM infection with at least one negative eligible randomised controlled trial of long acting beta-2-ago-
respiratory NTM culture; 2) use with caution if the patient nists.208 This included 40 patients with a primary outcome of
has significant hearing loss needing hearing aids or signifi- health related quality of life. It indicated improved quality of
cant balance issues. life with the use of budesonide/formoterol versus budesonide
30 Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463
BTS Guideline
alone. The Cochrane review identified significant methodolog- group compared with the control group. The mean difference
ical issues with this trial including inadequate and incorrectly in the ISWT, LCQ and SGRQ were all clinically important as
reported blinding and inadequate reporting of the data.208 they exceeded the mean clinically important difference (MCID)
for each outcome measure. These benefits were maintained at
Long acting anticholinergic agents 20 weeks (12 weeks post end of PR programme). Participants
There are no randomised controlled trials of long acting in the PR group were encouraged to continue with their exer-
muscarinic antagonists in bronchiectasis.209 Although studies cise programme after completion of the 8 week programme and
suggest that some patients with bronchiectasis will have signif- were offered free gym membership. However, no information
icant reversibility to anti-cholinergic bronchodilators, there is was collected on the intensity or frequency of exercise between
no evidence to establish that reversibility is a requirement for weeks 8–20 and so it is difficult to draw any conclusions on
benefit.210 the maintenance effect. Although this was a small trial, it was
sufficiently powered to detect a mean difference in the primary
endpoint (ISWT).
Short acting bronchodilators Lee et al (2014) conducted a well-powered RCT (n=85)
There are no randomised controlled trials to demonstrate if comparing an 8 week supervised exercise programme with a
short acting bronchodilators are beneficial in bronchiectasis.211 control group who received no intervention.150 Participants
As there are no large randomised controlled trials of broncho- were included if they reported dyspnoea on exertion (Modified
dilators in bronchiectasis there are limited data on the safety of Medical Research Council Dyspnoea (mMRC) score of ≥1). A
these agents. Data from COPD and asthma, however, suggests mMRC score of 1 equates to getting short of breath when hurrying
that they have an acceptable safety profile. on level ground or walking up a slight hill. Primary outcomes
were exercise capacity (ISWT and 6 min walking distance
Evidence statement (6MWD)) and health related quality of life Chronic Respira-
Long acting beta-2-agonists may be beneficial in patients with tory Disease Questionnaire (CRDQ). Secondary outcomes were
symptoms of breathlessness. (4) cough-related quality of life (LCQ) and psychological symptoms
Long acting anti-cholinergics in bronchiectasis may be benefi- (Hospital Anxiety and Depression Scale (HADS)). There was a
cial in patients with symptoms of breathlessness. (4) significant improvement in exercise capacity in the intervention
No evidence was identified to support the use of short acting group compared with the control group but these improvements
beta-2-agonists. (4) were not sustained at 6 or 12 months. There were also signifi-
Bronchodilator treatment may include short or long acting cant improvements in the dyspnoea and fatigue domains of the
beta-agonists, short or long acting anti-cholinergic bronchodila- CRDQ but not the domains of emotional function or mastery.
tors, or combined bronchodilators. There is no evidence to guide Exercise training did not have an effect on cough-related quality
which of these is the optimal strategy in bronchiectasis (4) of life or anxiety and depression. There was a statistically signif-
icant reduction in the frequency of acute exacerbations in the
exercise group (median 1 (IQR1-3)) compared with the control
Recommendations group (2 (1–3)) over 12 months (P=0.012). There was also a
➢➢ Use of bronchodilators in patients with bronchiectasis and
statistically significant longer time to first exacerbation in the
co-existing COPD or asthma should follow the guideline exercise group of 8 months (95% CI 7 to 9 months) compared
recommendations for COPD or asthma. (D) with the control group (6 months (95% CI 5 to 7 months)
➢➢ Offer a trial of long acting bronchodilator therapy in patients
P=0.047). However, these results should be interpreted with
with symptoms of significant breathlessness. (D) caution as a significant number of participants (30/85) that did
➢➢ Reversibility testing to beta-2-agonists or anticholinergic
not complete the 12 month follow-up.
bronchodilators may help to identify patients with co-ex- The most recent randomised controlled trial by Olveira et
isting asthma but there is no evidence to suggest that a al (2015) (n=30) aimed to assess the effect of a 12 week PR
response is required in order to benefit from bronchodila- programme versus a PR programme plus a hyperproteic oral
tors. (D) nutritional supplement.216 Exercise capacity was not a reported
outcome measure. Muscle strength measured using mean hand-
Pulmonary rehabilitation grip dynamometry was significantly improved in both groups at
Evidence summary 12 and 24 weeks. Health-related quality of life assessed using
A recent cross-sectional study by Bradley et al assessed the phys- the Quality of Life – Bronchiectasis questionnaire QOL-B Phys-
ical activity of participants with bronchiectasis (n-=63).212 Only ical Functioning scale significantly improved in the PR plus
11% of participants met the recommended physical activity nutritional supplement group but not in the PR alone group.
guidelines of ≥150 min of at least moderate activity per week.213 However, these results should be interpreted with caution for
There are four randomised controlled trials (RCTs) which inves- two main reasons. First, there was a large difference in the base-
tigate the effects of pulmonary rehabilitation (PR) in bronchi- line QOL-B score of the two groups. Although this was not a
ectasis.150 214–216 Mandal et al (2012) conducted a pilot RCT statistically significant difference, the mean QOL-B score of the
(n=30) comparing an 8 week PR programme plus respiratory PR alone group was more than 12 points lower than the PR plus
physiotherapy with respiratory physiotherapy alone.215 Respira- nutritional supplement group at baseline. In addition, between
tory physiotherapy was carried out twice daily using the oscil- group statistical analysis was not performed.
latory positive expiratory pressure (PEP) device the Acapella An uncontrolled, retrospective study by Van Zeller et al217
Choice. Outcome measures were the incremental shuttle walk (2012) assessed the effect of a 12 week PR programme on 41
test (ISWT), the endurance shuttle walk test (ESWT), the participants with bronchiectasis.217 The exercise component
Leicester Cough Questionnaire (LCQ) and the St George’s Respi- consisted primarily of cycle ergometer exercise with additional
ratory Questionnaire (SGRQ). After 8 weeks there was a signif- upper limb and quadriceps training. This does not reflect current
icant improvement in all outcome measures in the intervention UK clinical practice where PR programmes usually include
Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463 31
BTS Guideline
a walking component in order to improve walking function. Field walking tests
There was no significant change in 6MWD at the end of the Research has now been conducted to support the use of the
programme. These results are in direct contrast to the afore- 6MWT and ISWT as reliable and responsive measures of exer-
mentioned RCTs which all showed that exercise had a clinically cise capacity in the bronchiectasis population (Lee et al).220 This
significant effect on exercise capacity.150 214 215 study also found that there was a small learning effect in both
A larger (n=135) and more recent retrospective study evalu- measures at baseline and it is therefore recommended that two
ated the effect of a 3 week inpatient PR programme on individ- of each test are performed to accurately assess exercise capacity.
uals with bronchiectasis.218 This PR programme had a statistically In addition, a minimal important difference has been estimated
significant effect on 6MWD which improved by 35±43 m for the 6MWT (25 m) and ISWT (35 m) in bronchiectasis (Lee
(P<0.0001). Health-related quality of life was measured using et al).221 Therefore, these are suitable outcome measures to
the EuroQol visual analogue scale (EQ-VAS) and improved by assess exercise capacity before and after PR in the bronchiectasis
15±12 (P<0.0001). Dyspnoea was measured with the Baseline/ population.
Transition Dyspnoea Index (BDI/TDI) and this also improved
after the programme from 7.3±2.9 to 4±2.6 (no p value given).
Regression analyses revealed that male gender, baseline FEV1/ Evidence statements
VC<70% and>2 exacerbations in the previous year were inde- Pulmonary rehabilitation increases exercise capacity and can
pendent predictors of improvement in exercise capacity and improve quality of life in individuals with bronchiectasis. (1+)
health-related quality of life. Although this is a retrospective Pulmonary rehabilitation can reduce frequency of exacerba-
and uncontrolled study, it does reveal that patients with more tions over a 12 month period and can increase the time to first
severe bronchiectatic disease also benefit from inclusion in a PR exacerbation. (1-)
programme. IMT, when used in conjunction with pulmonary rehabilita-
There is currently no evidence assessing the incidence of cross tion, can enhance the longevity of the training effects. (1+)
infection of respiratory pathogens between individuals with IMT in isolation does not increase exercise capacity or quality
bronchiectasis in the group exercise setting. of life in individuals with bronchiectasis. (1-)
In summary, there is strong evidence from a number of trials 6MWT and ISWT are reliable and responsive outcome
to show that PR increases exercise capacity and can improve measures for use in bronchiectasis to evaluate exercise capacity
health-related quality of life in bronchiectasis. One RCT has also pre and post pulmonary rehabilitation. (3)
shown that PR reduces the frequency of acute exacerbations over There is currently no evidence assessing the incidence of cross
a 12 month period and increases the time to first exacerbation, infection of respiratory pathogens between individuals with
although there are significant methodological issues regarding bronchiectasis in the group exercise setting.
dropouts.150
Recommendations
➢➢ Offer pulmonary rehabilitation to individuals who are func-
Inspiratory muscle training tionally limited by shortness of breath (Modified Medical
Two studies investigate the effects of inspiratory muscle Research Council (MMRC) Dyspnoea Scale≥1). (B)
training (IMT).214 219 The study by Liaw et al219 found that ➢➢ Consider the use of inspiratory muscle training in conjunc-
an 8 week home-based IMT training programme resulted in tion with conventional pulmonary rehabilitation to enhance
a significant difference in inspiratory and expiratory muscle the maintenance of the training effect. (B)
strength in the intervention group when compared with the
control. However, there were no significant between group
differences in any other measure including pulmonary func- Good practice points
tion, quality of life or walking capacity. This study was at high ✓✓ Educate all individuals with bronchiectasis on the impor-
risk of bias due to significant differences between groups at tance of an exercise training programme.
baseline in some measures of pulmonary function and also age. ✓✓ Consider the 6MWT and/or the ISWT when evaluating
There were a relatively high number of drop outs and intention exercise capacity pre/post pulmonary rehabilitation in bron-
to treat analysis was not employed. There were 19 participants chiectasis. Prior to this, practice tests should be carried out
in each group but six participants dropped out in each group to eliminate any learning effect.
and therefore only 13 participants in each group were included ✓✓ Pulmonary rehabilitation providers should offer education
for final analysis. A final consideration is that the participants sessions tailored to the needs of individuals with bronchiec-
were not blinded as the control group did not receive any form tasis (eg, airway clearance techniques, the pathophysiology
of sham IMT. of bronchiectasis and relevant inhaled therapy).
The study by Newall et al214 was well-conducted but ✓✓ Pulmonary rehabilitation exercise and education sessions
had a small number of participants (n=32). 214 This study should be provided by appropriately qualified healthcare
had three groups: PR plus IMT, PR plus sham IMT and a practitioners.
control group which received no intervention. Exercise Further information on Pulmonary rehabilitation is provided
capacity increased significantly in both the PR-SHAM and in the BTS Quality Standards for Pulmonary rehabilitation
PR-IMT groups. HRQOL was significantly better in the (https://www.b rit- t horacic.o rg.u k/ s tandards-o f- c are/ q uality-
PR-IMT group than the PR-SHAM. After 3 months, exercise standards/bts-pulmonary-rehabilitation-quality-standards/)
capacity had declined significantly in the PR-SHAM group
but had been maintained in the PR-IMT group. The findings Research recommendation
of this study suggest that there is no additional advantage The role of education, self management plans and who delivers
of simultaneous IMT with PR to increase exercise capacity. the pulmonary rehabilitation needs to be explored.
However, IMT may be important in prolonging the benefit The role of pulmonary rehabilitation after exacerbations
of the training effects. requiring hospital admission needs to be explored.
32 Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463
BTS Guideline
The incidence of cross-infection of respiratory pathogens in persistent infection with P. aeruginosa and the extent of residual
the group exercise setting should be investigated in the bronchi- bronchiectasis after surgery have been associated with a signifi-
ectasis population. cantly shorter recurrence-free interval.232 The primary cause of
bronchiectasis may influence post-surgical outcomes with likely
better outcomes after post obstructive bronchiectasis and poorer
What is the role of surgery in managing bronchiectasis?
outcomes in immunodeficiency.232 There are however limited
Multiple case series of surgical resection for bronchiectasis are
data to guide clinicians in defining risk benefit ratios.229 238 Even
available.222–237 A Cochrane review concluded there are no high
when the primary cause of bronchiectasis persists, successful
quality randomised control studies and the benefits of surgery
outcomes are reported. Surgery can be successful in primary
over conservative management were unclear. It is also likely
ciliary dyskinesia.226
there is a reporting bias for the available case series.238
Freedom from symptoms of bronchiectasis have reported as
Generally surgery should not be considered until there is
high as 61%–84% when followed up from between 1 to 5 years
optimisation of medical management. With this caveat the
or more post-operatively.224 225 234
consistency of available evidence supports a role for surgery in
bronchiectasis in selected patients.
The indications for surgical resection in bronchiectasis include Evidence statement
ºº persistent symptoms despite up to a year of comprehen- Surgery may be successful in bronchiectasis in reducing exacer-
sive medical treatment, bations or treating haemoptysis. (3)
ºº exacerbations that are either severe or frequent and inter- The ideal candidate(s), timing for surgery and operative approach
fere with social/professional life, remain ill-defined. (3)
ºº recurrent refractory or massive haemoptysis, Video assisted thoracoscopic technique can provide outcomes at
ºº post obstruction bronchiectasis distal to tumours least as successful as open surgery. (3)
ºº localised severely damaged lobe/segment that may be a Improvements in bronchiectasis symptoms can be seen after
source of sepsis that left in situ may lead to extension of surgery for bilateral disease. (3)
lung damage.
Surgery is generally applied when there is focal disease in the
Recommendations
presence of the above clinical scenarios. Therefore the popula-
➢➢ Consider lung resection in patients with localised disease
tion both requiring and suitable for surgery is likely to be small.
whose symptoms are not controlled by medical treatment
Notably many series reported to date included patients with
optimised by a bronchiectasis specialist. (D)
a lower mean age than seen in many clinics, ranging from 30
➢➢ Offer multidisciplinary assessment, including a bronchi-
to 48 years of age.222 225 239 The median duration of symptoms
ectasis physician, a thoracic surgeon and an experienced
prior to surgery in the reported series was usually prolonged e.g.
anaesthetist, of suitability for surgery and pre-operative
6 years.225
assessment of cardiopulmonary reserve post resection. (D)
A variety of operative techniques have been described. In expe-
rienced hands video assisted thoracoscopic (VAT) performs as
well as open surgery231 233 239 and may be associated with lower Good practice point
rates of complications such as blood loss and shorter hospital- ✓✓ Consider nutritional support and pre-operative pulmonary
isations.233 There is however an intraoperative conversion rate rehabilitation before surgical referral.
from VATS to open surgery of up to 12%.233 The resection limits
range from segmentectomy to pneumonectomy but the available Lung transplantation for bronchiectasis
literature does not provide robust decision making tools to aid Lung transplantation is an effective therapy for bronchiectasis
decision making on the optimal resection limits in day to day when maximal medical therapy is failing. Lung transplantation
practice.222 225 231 233 239 is generally reserved for those with diffuse bilateral disease and
With this in mind pre-surgical safety assessment should be bilateral transplantation is then performed. There are however
undertaken to define the expected amount of residual lung, reports of single lung transplantation with contralateral pneumo-
underlying cardiopulmonary reserve and anticipated overall nectomy. Generally lung transplantation is felt indicated where
risks. Pulmonary rehabilitation and optimisation of nutrition are survival is anticipated at 50% at 2 years without lung transplan-
important aspects with which respiratory physicians can support tation.241 International guidelines note the risks of transplanta-
their patients. tion in general appear to increase with age and generally patients
In the available series the 60 day mortality outcomes ranged above the age of 65 are felt to have an unfavourable risk: benefit
from 0%–11%.224 232 237 239 Common post-operative compli- mortality ratio.241
cations included wound infection, empyema, systemic sepsis, Internationally bronchiectasis is reported as a rare indication
post thoracotomy pain, prolonged air leak and recurrence of for lung transplantation representing less than 5% of all bilat-
bronchiectasis.224–226 234 235 Early morbidity rates ranged from eral lung transplantations recorded in the international registry.
13% to 24%222 225 232 235 239 with wound infection reported as Overall less than 1200 transplant procedures for bronchiectasis
the most common complication (6%) in one large series of 277 were recorded in the international registry as compared with
patients.240 1280 for pulmonary hypertension, 6862 for cystic fibrosis and
For long term complications the recurrence rate is likely to 13 672 for COPD (https://www.ishlt.org/registries/slides.asp?
depend on the completeness of resection and underlying aeti- slides=heartLungRegistry accessed Aug 2015).
ology of bronchiectasis. Perceived complete resection is asso- The available case series focus on lung transplantation for
ciated with significantly better long term outcomes than cases adults with bronchiectasis with no significant data reported
where incomplete resection has occurred.223 225 232 239 240 In one for paediatric transplantation. While collectively less than 200
small case series of 31 patients, the mean time to recurrence of patients, these case series report good outcomes following trans-
symptoms was 34 months.232 An immunocompromised status, plantation. In a case series of 22 patients transplanted in the
Table 6 Common organisms associated with acute exacerbation of bronchiectasis and suggested antimicrobial agents- adults
Length of Length
Organism Recommended first line treatment treatment Recommended second line treatment of treatment
Streptococcus pneumoniae Amoxicillin 14 days Doxycycline 100 mg BD 14 days
500 mg Three times a day
Haemophilus influenzae- beta lactamase Amoxicillin 14 days Doxycycline 100 mg BD 14 days
negative 500 mg Three times a day Or
Or Ciprofloxacin
Amoxicillin 500 mg or 750 mg BD
1G Three times a day Or
Or Ceftriaxone 2G OD (IV)
Amoxicillin 3G BD
Haemophilus influenzae- beta lactamase Amoxicillin with clavulanic acid 625 14 days Doxycycline 14 days
positive one tablet Three times a day 100 mg bd
Or
Ciprofloxacin
500 mg or 750 mg BD
Or
Ceftriaxone 2G OD (IV)
Moraxella catarrhalis Amoxicillin with clavulanic acid 625 14 days Clarithromycin 500 mg BD 14 days
one tablet Three times a day Or
Doxycycline 100 mg BD
Or
Ciprofloxacin
500 mg or 750 mg BD
Staphylococcus aureus (MSSA) Flucloxacillin 14 days Clarithromycin 14 days
500 mg Four times a day 500 mg BD
Or
Doxycycline 100 mg BD
Or
Amoxicillin with clavulanic acid 625 one tablet Three
times a day
Staphylococcus aureus (MRSA) Doxycycline 100 mg BD 14 days Third line 14 days
Oral preparations Rifampicin (<50 Kg) Linezolid
450 mg OD 600 mg BD
Rifampicin (>50 Kg)
600 mg OD
Trimethoprim
200 mg BD
Staphylococcus aureus (MRSA) Vancomycin 1 gm BD* (monitor serum 14 days Linezolid 14 days
Intravenous preparations levels and adjust dose accordingly) or 600 mg BD
Teicoplanin 400 mg OD
Coliforms for example, Klebsiella, enterobacter Oral Ciprofloxacin 14 days Intravenous 14 days
500 mg or 750 mg BD Ceftriaxone
2G OD
Combination therapy
The above can be combined with gentamicin or
tobramycin or
Colistin 2MU TDS (under 60 kg, 50 000–75 000 Units/kg
daily in 3 divided doses)
Symptoms of Rhinosinusitis
• Nasal Discharge/congestion
• Nasal blockage/obstruction Features suggesting alternative
• Anterior/post nasal drip diagnosis
• Facial pain/pressure
• Hyposmia/anosmia – Unilateral symptoms
– Bleeding/bloody discharge
– Crusting
– Orbital symptoms
– Severe frontal headache
– Frontal swelling
– Neurological symptoms
Trial of nasal steroids and irrigation
Several studies have shown a higher than expected prevalence patients with bronchiectasis alone, and the frequency of colo-
of bronchiectasis in patients with COPD and these patients prob- nising organisms such as P. aeruginosa and H. influenzae was
ably have a worse prognosis than bronchiectasis without COPD; similar. Longitudinal data were available for a small cohort of
however there is an acknowledged lack of evidence as to impli- patients with RA and bronchiectasis. In these patients, control
cations for treatment.255 269 330–332 of RA disease activity appeared to track with spirometry, in that
Patients with HIV-related disease appear to be at greater risk spirometry declined when the DAS score rose, and vice versa.
of bronchiectasis than the general population but management DMARDs did appear to be associated with increased pneumonia
implications were not discussed in the studies reviewed.333 334 and other infections.
The risk of infection in patients using DMARDs or biologics
was assessed in a cohort of >3000 patients, of whom 86 had
Inflammatory bowel disease both a rheumatological disease and bronchiectasis.337 Sufficient
The majority of studies are undermined by low numbers, which data was available on only 47 patients receiving DMARDs or
may reflect the relatively small population of patients with bron- biologics. Of 40 patients with RA and bronchiectasis, 35 were
chiectasis whose condition is associated with inflammatory bowel seropositive. 13 had bronchiectasis prior to RA, 27 were diag-
disease (IBD) (see online appendix 6 <1%–3%)23 62 Kelly et al nosed with bronchiectasis after the onset of RA but it was
studied 10 patients (time period not stated)59 and Mahadeva et al attributed directly to RA only in 13 cases, otherwise the aeti-
identified 17 patients over a 14 year period with coexistent IBD ology was thought to be childhood infection. An OR of 8.7 (95%
and pulmonary disease.60 Bronchiectasis appeared to be the most CI 1.7 to 43.4) was found for respiratory infections in patients
common feature although other abnormalities were seen on CT treated with biologics compared with traditional DMARDs. The
scan. In some cases a biopsy revealed evidence of lymphocytic OR for infections was 7.4 (2.0–26.8) in the presence of previous
inflammation59 and a useful clinical response to oral or inhaled sputum colonisation by potentially pathogenic micro-organ-
corticosteroids was observed.60 The nature of the steroid treat- isms. The authors therefore recommended using non-biologics
ment and its outcome were not described in detail although alve- in preference to biologics if possible. Etanercept and rituximab
olitis and bronchiolitis were reported to resolve fully.60 were associated with a lower rate of infections than the other
The overlap of IBD and bronchiectasis was comprehensively biologics, but the numbers were very small in this study.
reviewed in a European Respiratory Monograph in 2011, again
with an emphasis on corticosteroid responsiveness although the
lack of evidence was acknowledged.335 Evidence statements
Patients with bronchiectasis and comorbid COPD have more
severe disease and worse prognosis than those with bronchiec-
Rheumatoid arthritis tasis alone. (2+)
In a study of the effects of immunosuppression, 37 patients with Patients with co-morbid rheumatoid arthritis and bronchiectasis
rheumatic diseases (and nine with IBD) were identified in a data- may have worse outcome than those with either disease alone. (3)
base of 539 patients with bronchiectasis: 26 had rheumatoid Immunosuppressive treatment for connective tissue disorders
arthritis (RA).336 The majority developed bronchiectasis after the is associated with a higher risk of infection in general; biologics
onset of autoimmune disease. All had received either conven- may promote infections more than traditional DMARDs, and
tional disease modifying anti-rheumatic drugs (DMARDs) - the risk may be higher in patients already colonised with poten-
mostly methotrexate - or biologics. Methotrexate in particular tially pathogenic micro-organisms. (3)
was associated with a range of adverse effects. Patients with Inflammatory bowel disease-related bronchiectasis may be
RA or IBD were not found to suffer more exacerbations than responsive to corticosteroids. (3)
Hill AT, et al. Thorax 2019;74(Suppl 1):1–69. doi:10.1136/thoraxjnl-2018-212463 43
BTS Guideline
Appendix 4: Specialist immunological investigations or subcutaneous immunoglobulin replacement therapy results in a clinically
(immunology services only) meaningful reduction in bacterial chest infections [22 23].
The prevalence of deficiency in one or more IgG subclasses in patients with
Specialist immunological tests are required in a small proportion of patients bronchiectasis ranges from 6 to 48% [1 7 24-27]. Discrepancy between studies
with bronchiectasis to make a diagnosis of primary immune deficiency, classify is largely explained by differences in criteria used to define IgG subclass deficiency
distinctive disease variants or to stage the extent of immune deficiency. Detailed and inclusion of reduced IgG4 concentration which is not regarded as a marker of
investigation of the immune system should be undertaken by diagnostic humoral immune deficiency [2]. The prevalence of IgG1, IgG2, or IgG3 deficiency
laboratories which are externally accredited by appropriate regulatory bodies in patients with bronchiectasis is less than 1% in studies using more stringent
using validated standardized laboratory tests and a definitive diagnosis of criteria to define this condition [24 25 27].
immune deficiency should be based on established and accepted criteria[1-3]. The clinical significance of isolated reduction in IgG1, IgG2 and IgG3 should
Clinicians should be aware that some laboratory tests of immune function are be confirmed by Pneumovax II test immunisation in patients with low baseline
not quality assured and that definitive guidelines of diagnosis of primary immune pneumococcal antibody levels [2]. IgG subclass deficiency is associated with an
deficiencies may be modified as our understanding of the immune system increased risk of sino-pulmonary infection in patients with selective IgA deficiency
increases. (IgA concentration less than 0.07g/L) and measurement of IgG subclasses should
be considered in patients with co-existing defects in pneumococcal vaccine
Enumeration of T and B cell counts in the diagnosis of primary responses and composition of memory B cell subsets [28-30]. Measurement of
and secondary antibody deficiency syndrome IgG subclasses should also be considered in patients with a clinical suspicion of
Analysis of B and T cell counts plays an important role in diagnosis of a number activated PI(3)Kδ (APDS) syndrome [19 20]. Assessment of IgG subclasses may
of primary and secondary immune deficiencies which are associated with also be considered in patients with impaired pneumococcal vaccine responses to
bronchiectasis. Reduced B cell counts can be seen in patients with CVID [3], distinguish between specific polysaccharide antibody and IgG subclass deficiency
reduced or absent B cell numbers are characteristic features of thymoma and even though principles of management for both disorders are very similar [2].
immune deficiency [4], and also occur in 45% of patients with rituximab induced
symptomatic antibody deficiency [5 6]. There is evidence that some patients Assessment of MBL genotype and function
with idiopathic bronchiectasis may have reduced B cell counts, however clinical Mannose binding lectin (MBL) is an innate immune protein which recognizes cell
significance and implications for management await further studies [7 8]. Low surface carbohydrates expressed by a wide variety of bacteria, viruses and fungi
CD4 T cell counts may be observed in patients with HIV-1 infection, CVID, and [31]. MBL activates the lectin complement pathway resulting in opsonisation
thymoma with immune deficiency [3 5]. and phagocytosis of microorganisms and may also contribute to resolution
of inflammation in the lung by increased elimination of apoptotic cells and
Analysis of naive and memory B and T cell proportions in suppression of inflammatory immune responses. Genetic polymorphisms in the
classification of patient with primary immune deficiencies and MBL exon and promoter region influence MBL concentration and function. MBL
deficiency is common (10-30% of population depending on the definition used)
selection of individual patients for further genetic testing
[32] but as yet there is no evidence that MBL deficiency increases susceptibility to
Measurement of class switched memory B cell and of naïve CD4 T cell percentages
infection [32] although it may modify disease course in patients with co-existing
have been incorporated into recent ESID guidelines for the diagnosis of CVID [9].
inherited or acquired immune deficiencies [31]. For example there is a higher
A marked reduction in naïve CD4 T cell proportion (less than 10%) in conjunction
rate of bronchiectasis in CVID if MBL deficiency is also present [33 34], and
with low CD4 T cell counts (less than 200 cells/ul) in patients with a history of
meta-analysis of 12 studies of 2863 adult patients with cystic fibrosis showed an
opportunistic T cell associated infections or significant granulomatous disease
association between low expressing MBL genotypes and earlier age of onset of
should raise the possibility of late onset combined immunodeficiency (LOCID)
Pseudomonas aeruginosa infection, chronic Burkholderia cepacia colonisation,
[10]. Identification of this patient group should prompt further investigations
impaired lung function, need for lung transplantation and/or mortality [35].
using next generation sequencing technology for gene mutations causing immune
Only 2 studies have examined the relationship between MBL deficiency and
deficiency. In a large multi-centre French study of CVID patients the prevalence of
severity of lung disease in non-CF bronchiectasis. McFarlane and colleagues
bronchiectasis in patients with LOCID receiving IgG therapy was significantly higher
showed in a retrospective cohort that there was no association between reduced
than that observed in CVID patients which implies that a T cell defect may also
serum MBL concentrations and severity of lung disease [36]. In contrast a larger
be a contributory factor to development of progressive lung disease. Assessment
prospective study showed low expressing MBL genotypes were associated with
of memory B cell proportions has been used to classify patients with CVID into
increased bacterial colonisation, infective exacerbations and hospital admissions,
homogeneous disease groups and potentially select individual patients for further
more severe CT scores, worse quality of life and increased airway inflammation
genetic testing [11]. Reduced memory B cell subsets have been linked to increased
compared to patients with intermediate and high expressing MBL genotypes [34].
rates of bronchiectasis in CVID patients [8 12-15] and poorer pneumococcal
Confirmation of these findings in further studies and evidence that improvement
serotype vaccine responses[16 17] . Expansion of terminally differentiated CD8
in MBL function influences clinical outcomes are needed before this test can be
T cells in response to persistent EBV and/or CMV viraemia, reduced naïve CD4 T
recommended in routine investigation of patients with bronchiectasis.
cell and memory CD27+ B cells are characteristic features of patients with gain of
function in the gene encoding p110δ subunit of phosphatidylinositol-3-OH kinase
(PI (3) K) who may potentially benefit from rapamycin or PI(3)K inhibitor therapy Assessment of Haemophilus influenzae Type B (HIB) and
[18 19]. tetanus toxoid antibodies
Measurement of serum levels of antigen-specific IgG antibody to vaccine antigens
Measurement of IgG subclasses or documented infection is essential for diagnosis of primary antibody deficiency
IgG subclass deficiency is associated with increased susceptibility to bacterial [1]. Evaluation of functional antibody responses should include measurement
sino-pulmonary infection and bronchiectasis, but the clinical value of measuring of antibody levels to T cell dependent protein or glycoprotein antigens and T
IgG subclasses is controversial and it is not usually recommended in the initial cell independent polysaccharide antigens [1 9]. In clinical practice analysis of
investigation of patients with suspected antibody deficiency [2]. Available tests T cell dependent antibody function is usually assessed by analysis of tetanus
to measure IgG subclasses are not standardised [20]. Concentrations of IgG2 toxoid antibodies (protein antigen) or Haemophilus influenzae Type B (HIB)
and IgG3 are influenced by genetic variation in composition of IgG heavy chains polysaccharide capsule antigen coupled to a carrier protein (conjugate vaccine).
and steroid therapy [21 22]. Reduced levels of individual IgG subclasses are not Protective antibody levels to tetanus toxoid (0.15IU/mL) and to HIB polysaccharide
uncommon in healthy controls and not necessarily associated with an increased capsule (1ug/mL) have been established [3 37 38]. Antibody levels below protective
risk of bacterial infection [21]. In addition low IgG subclasses may spontaneously thresholds following test immunisation are believed to indicate impaired vaccine
recover which means that reduced IgG subclass values should be confirmed by responses and a functional antibody deficiency syndrome.
two tests at least 1 month apart [2 21]. Antibody responses to polysaccharide are A number of studies have examined the clinical utility of measurement of baseline
not exclusively restricted to IgG2 subclasses [21] and there are very limited data and post vaccination HIB antibody levels in the diagnosis of immune deficiency
to suggest to suggest that correction of IgG subclass deficiency using intravenous in patients with bronchiectasis [25 26 39 40]. Reduced HIB vaccine responses
Age yrs Mean 52.7 (Range 13-82) Mean 12.1 (Range 3.1-18.1) Mean 49 (Range 17-87)
Aetiology Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%)
10 +/- Sweat test CFT
CFTR gene analysis (Panel
covering 86% of local 146 CFTR gene analysis Sw
disease causing mutations) 1 +/+
Pre-excluded by sweat test and genetic analysis with selected measurement of
Cystic fibrosis 4 (2.7) 165 2 +/+ 2 (1.2)
nasal potential difference and faecal elastase
Sweat sodium chloride
equivalent (only in those
11 4
patients with at least one
CFTR mutation)
Se
Aspergillus specific IgE 150 28 Total IgE
Anti-pneumococcal Antigen/mitogen
150 25
Humoral immunodeficiency antibody titre 12 (8.0) stimulation tests 110 46 46 (42.0) 165 7 (4.2)
Staphyloococcal and
candida killing ability
tests
Neutrophil adhesion
150 0
markers
Defect in neutrophil function 1 (0.7) Not investigated Not investigated
Neutrophil respiratory burst 150 2
Rhe
Autoantibodies
AN
Autoimmunity Not investigated Not investigated including rheumatoid 165 3 (1.8)
factor
Sel
CCP
24h oesophageal pH
51 23 23 (45.0)
monitoring
Aspiration Not investigated 6 (4.0) Not investigated 2 (1.0)
Barium meal 18 2 1 (5.5)
(Continued )
References
1. Pasteur MC, Helliwell SM, Houghton SJ, et al. An investigation into causative factors in patients with bronchiectasis. American Journal of Respiratory & Critical Care Medicine 2000;162(4 Pt 1):1277-84
2. Li AM, Sonnappa S, Lex C, et al. Non-CF bronchiectasis: does knowing the aetiology lead to changes in management? European Respiratory Journal 2005;26(1):8 -14
3. Shoemark A, Ozerovitch L, Wilson R. Aetiology in adult patients with bronchiectasis. Respiratory medicine 2007;101(6):1163 -70
4. McShane PJ, Naureckas ET, Strek ME. Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture. Chest 2012;142(1):159 -67 doi: http://dx.doi.org/10.1378/chest.11 -1024[published Online First: Epub Date]|.
5. Anwar GA, McDonnell MJ, Worthy SA, et al. Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study. Respiratory medicine 2013;107(7):1001 -7 doi: http://dx.doi.org/10.1016/j.rmed.2013.04.013[published Online First
6. Lonni S, Chalmers JD, Goeminne PC, et al. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Annals of the American Thoracic Society 2015;12(12):1764 -70 doi: 10.1513/AnnalsATS.201507 -472OC[published Online First:
7. Qi Q, Wang W, Li T, et al. Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population: A prospective study. Respirology 2015;20(6):917 -24 doi: 10.1111/resp.12574[published Online First: Epub Date]|.
Appendix 5 (Continued )
Li et al 2005 [2] Shoemark et al 2007 [3] McShane et al 2012 [4] Anwar et al 2013 [5] Lon
UK tertiary clinic UK tertiary clinic USA University referral centre UK and Ireland - 2 general bronchiectasis clinics 9 European U
Mean 12.1 (Range 3.1-18.1) Mean 49 (Range 17-87) Mean 61.4 (1SD = 17.7) Mean 66.1 (Range 24-89) Med
ation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Perfor
Sweat test CFTR gene analysis 4 +/- CFTR gene analysis
CFTR gene analysis 94
CFTR gene analysis Sweat test 1 +/+ 1 (0.6) Sweat test
Sweat test 12
by sweat test and genetic analysis with selected measurement of
165 2 +/+ 2 (1.2) 15 0 (0)
nasal potential difference and faecal elastase
Only investigated in the presence of high risk clinical features or if no other apparent
Only investigated
aetiology. 100 patients were screened.
A1AT levels 106 5 12 (11.3) another A1AT levels A1AT deficiency evaluated if family
Not investigated Not investigated cause was identified 169 2 (1.2)
A1AT phenotype 106 11 in 10 patients A1AT phenotype Not specified
Pasteur et al 2000 [1] Li et al 2005 [2] Shoemark et al 2007 [3] McShane et al 2012 [4]
66 19 Saccharin test Only investigated
Study site UK tertiary clinic UK tertiary clinic UK tertiary clinic USA University referral centre
Subjects with bronchiectasis 150 adults 136 children 165 adults 112 adults
Nasal NO and Sacharrin
Nasal nitric oxide
M:F 56:94 65:71 28:107 test
32:80
de (only in 19 (29.0) 165 17 (10.3) Not specified 3 (2.8) Referred for investigation if history was suggestive 2 (1.1)
Age yrs Mean 52.7 (Range 13-82) Mean 12.1 (Range 3.1-18.1) Mean 49 (Range 17-87) Mean 61.4 (1SD = 17.7)
with 19 9
y function) FEV1
Cilial%brushings for LM Mean 74 Mean 71 Mean 72 Mean 75
Referral to specialist centre
and EM Aetiology Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%)
10 +/- Sweat test CFTR gene analysis
CFTR gene analysis (Panel CFTR
covering 86% of local 146 Selected patients with asthma, central bronchiectasis, peripheral eosinophilia and CFTR gene analysis Sweat test
Total IgE disease causing mutations) 1 +/+ Aspergillus specific IgG 164 44 Total IgE
Total IgE >1000 ng/mL
Pre-excluded by sweat test and genetic analysis with selected measurement of
Swe
Cystic fibrosis 4 (2.7) 165 2 +/+ 2 (1.2) 15 0 (0)
nasal potential difference and faecal elastase
Sweat sodium chloride
Sputum and/or blood equivalent (only in those On
patients with at least one
11 4 Skin prick tests Skin prick tests 61 11 Aspergillus specific IgE
eosinophilia
CFTR mutation)
Not investigated 165 13 (7.8) 7 (4.3) 12
A1AT levels 150 2 1 (0.9) A1AT levels 106 5 12 (11.3) another A1A
Serum precipitins Serum IgE Serum precipitins
Alpha-1 antitrypsin deficiency 0 (0.0) Not investigated Not investigated cause was identified
A1AT ZZ phenotype 150 0 A1AT phenotype 106 11 in 10 patients A1A
Aspergillus specific IgE
Blood eosinophilia
Ciliary function 66 19 Saccharin test
Neutrophil adhesion
Autoantibodies 150 0 Rheumatoid factor, Anti-
markers ANA ANA 179 13
Not investigated including
Defect rheumatoid
in neutrophil function 165 3 (1.8) 1 (0.7) 106 Not investigated
20 with Not investigated CCP
Not investigated
References
1. Pasteur MC, Helliwell SM, Houghton SJ, et al. An investigation into causative factors in patients with bronchiectasis. American Journal of Respiratory & Critical Care Medicine 2000;162(4 Pt 1):1277 -84
rnal of Respiratory & Critical Care Medicine 2000;162(4 Pt
2. 1):1277 -84 S, Lex C, et al. Non-CF bronchiectasis: does knowing the aetiology lead to changes in management? European Respiratory
Li AM, Sonnappa Journal 2005;26(1):8 -14
espiratory Journal 2005;26(1):8 -14 3. Shoemark A, Ozerovitch L, Wilson R. Aetiology in adult patients with bronchiectasis. Respiratory medicine 2007;101(6):1163 -70
4. McShane PJ, Naureckas ET, Strek ME. Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture. Chest 2012;142(1):159 -67 doi: http://dx.doi.org/10.1378/chest.11 -1024[published Online First: Epub Date]|.
5. Anwar GA, McDonnell MJ, Worthy SA, et al. Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study. Respiratory medicine 2013;107(7):1001 -7 doi: http://dx.doi.org/10.1016/j.rmed.2013.04.013[published Online First: Epub Date]|.
re. Chest 2012;142(1):159 -67 doi: http://dx.doi.org/10.1378/chest.11 -1024[published
6. Lonni S, Chalmers JD, Goeminne PC, etOnline First:
al. Etiology Epub Date]|.
of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Annals of the American Thoracic Society 2015;12(12):1764 -70 doi: 10.1513/AnnalsATS.201507 -472OC[published Online First: Epub Date]|.
al cohort study. Respiratory medicine 2013;107(7):1001 -77. doi: http://dx.doi.org/10.1016/j.rmed.2013.04.013[published
Qi Q, Wang Online First:
W, Li T, et al. Aetiology and clinical characteristics of patients with bronchiectasis EpubHan
in a Chinese Date]|.
population: A prospective study. Respirology 2015;20(6):917 -24 doi: 10.1111/resp.12574[published Online First: Epub Date]|.
verity. Annals of the American Thoracic Society 2015;12(12):1764 -70 doi: 10.1513/AnnalsATS.201507 -472OC[published Online First: Epub Date]|.
pective study. Respirology 2015;20(6):917 -24 doi: 10.1111/resp.12574[published Online First: Epub Date]|.
Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%) Investigation Performed n Abnormal n Diagnostic n (%)
4 +/- CFTR gene analysis
Not investigated
Only investigated if suggestive signs and symptoms Only investigated if suggestive signs and symptoms
Total IgE
24 Serum immunoglobulins
Serum immunoglobulins
55 Serum electrophoresis
45
79
2 (1.1) 1258 73 (5.8) 476 23 17 3.6)
28 9 (4.9) Investigated if clinical features of rheumatological disease Investigated if clinical features of rheumatological disease
Adults
[2] 1995 USA 123 42% 4% 4% 30%
[3] 1996 UK 49 12% 4% 12% 71%
References
1. Scala RA, D.;Palumbo, U.;Montella, L.;Giacobbe, R.;Martucci, P.;Del Prato, B. Prevalence, age distribution and aetiology of bronchiectasis: a retrospective study on 144 symptomatic patients. Monaldi Archives for Chest Disease 2000;55(2):101-5
2. Nicotra MB, Rivera M, Dale AM, et al. Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort. Chest 1995;108(4):955-61
3. Evans SA, Turner SM, Bosch BJ, et al. Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. European Respiratory Journal 1996;9(8):1601-4
4. Horvath IL, S.;Wodehouse, T.;Kharitonov, S. A.;Cole, P. J.;Barnes, P. J. Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress. Thorax 1998;53(10):867-70
5. Tsang KW, Lam SK, Lam WK, et al. High seroprevalence of Helicobacter pylori in active bronchiectasis. American Journal of Respiratory & Critical Care Medicine 1998;158(4):1047-51
6. Cuvelier AM, J. F.;Hellot, M. F.;Benhamou, D.;Martin, J. P.;Benichou, J.;Sesboue, R. Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis. Chest 2000;117(2):415-9
7. Pasteur MC, Helliwell SM, Houghton SJ, et al. An investigation into causative factors in patients with bronchiectasis. American Journal of Respiratory and Critical Care Medicine 2000;162(4 pt1):1277-84
8. Caballero ED, M. E.;Perez, M. T.;Manresa, J. M.;Ferrer, A.;Orriols, R. Anti-Pseudomonas aeruginosa antibody detection in patients with bronchiectasis without cystic fibrosis. Thorax 2001;56(9):669-74
9. Angrill J, Agusti C, de Celis R, et al. Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors. Thorax 2002;57(1):15-9
10. Palwatwichai A, Chaoprasong C, Vattanathum A, et al. Clinical, laboratory findings and microbiologic characterization of bronchiectasis in Thai patients. Respirology 2002;7(1):63-6
11. Kelly MG, Murphy S, Elborn JS. Bronchiectasis in secondary care: a comprehensive profile of a neglected disease. Eur J Intern Med 2003;14(8):488-92
12. Tsang KW, Tipoe GL, Mak JC, et al. Ciliary central microtubular orientation is of no clinical significance in bronchiectasis. Respiratory medicine 2005;99(3):290-7
13. Shoemark A, Ozerovitch L, Wilson R. Aetiology in adult patients with bronchiectasis. Respiratory medicine 2007;101(6):1163-70
14. Martinez-Garcia MA, Soler-Cataluna JJ, Perpina-Tordera M, et al. Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis. Chest 2007;132(5):1565-72
15. Onen ZP, Gulbay BE, Sen E, et al. Analysis of the factors related to mortality in patients with bronchiectasis. Respiratory medicine 2007;101(7):1390-7 doi: 10.1016/j.rmed.2007.02.002[published Online First: Epub Date]|.
16. Steinfort DP, Brady S, Weisinger HS, et al. Bronchiectasis in Central Australia: a young face to an old disease. Respiratory medicine 2008;102(4):574-8
17. Bhatta N, Dhakal SS, Rizal S, et al. Clinical spectrum of patients presenting with bronchiectasis in Nepal: evidence of linkage between tuberculosis, tobacco smoking and toxic exposure to biomass smoke. Kathmandu University medical journal
2008;6(2):195-203
18. Murray MP, Pentland JL, Turnbull K, et al. Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis. European Respiratory Journal 2009;34(2):361-4 doi: http://dx.doi.org/10.1183/09031936.00163208[published Online First: Epub Date]|.
19. King PT, Holdsworth SR, Farmer M, et al. Phenotypes of adult bronchiectasis: onset of productive cough in childhood and adulthood. Copd: Journal of Chronic Obstructive Pulmonary Disease 2009;6(2):130-6 doi: http://dx.doi.
org/10.1080/15412550902766934[published Online First: Epub Date]|.
20. Guilemany JM, Angrill J, Alobid I, et al. United airways again: high prevalence of rhinosinusitis and nasal polyps in bronchiectasis. Allergy 2009;64(5):790-7 doi: http://dx.doi.org/10.1111/j.1398-9995.2008.01892.x[published Online First: Epub Date]|.
21. Loebinger MR, Wells AU, Hansell DM, et al. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. European Respiratory Journal 2009;34(4):843-9 doi: http://dx.doi.org/10.1183/09031936.00003709[published Online
First: Epub Date]|.
22. Ergan Arsava B, Coplu L. Does airway colonization cause systemic inflammation in bronchiectasis? Tuberkuloz ve Toraks 2011;59(4):340-7
23. Habesoglu MA, Ugurlu AO, Eyuboglu FO. Clinical, radiologic, and functional evaluation of 304 patients with bronchiectasis. Annals of thoracic medicine 2011;6(3):131-6 doi: http://dx.doi.org/10.4103/1817-1737.82443[published Online First: Epub Date]|.
BTS Guideline
63
64
Appendix 6 (Continued )
24. Devaraj A, Wells AU, Meister MG, et al. Pulmonary hypertension in patients with bronchiectasis: prognostic significance of CT signs. AJR. American journal of roentgenology 2011;196(6):1300-4 doi: http://dx.doi.org/10.2214/AJR.10.5221[published Online
First: Epub Date]|.
25. McShane PJ, Naureckas ET, Strek ME. Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture. Chest 2012;142(1):159-67 doi: http://dx.doi.org/10.1378/chest.11-1024[published Online First: Epub Date]|.
26. Gale NS, Bolton CE, Duckers JM, et al. Systemic comorbidities in bronchiectasis. Chronic respiratory disease 2012;9(4):231-8 doi: http://dx.doi.org/10.1177/1479972312459973[published Online First: Epub Date]|.
27. Macfarlane JG, Jary H, Hester KL, et al. Low serum mannose-binding lectin level is not associated with disease severity in non-cystic fibrosis bronchiectasis. Innate immunity 2012;18(6):787-92 doi: http://dx.doi.org/10.1177/1753425912440472[published
Online First: Epub Date]|.
BTS Guideline
28. Jacques PS, Gazzana MB, Palombini DV, et al. Six-minute walk distance is not related to quality of life in patients with non-cystic fibrosis bronchiectasis. Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E
Tisilogia 2012;38(3):346-55
29. Goeminne PC, Scheers H, Decraene A, et al. Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients. Respiratory research 2012;13:21 doi: http://dx.doi.
org/10.1186/1465-9921-13-21[published Online First: Epub Date]|.
30. Giron Moreno RM, Fernandes Vasconcelos G, Cisneros C, et al. Presence of anxiety and depression in patients with bronchiectasis unrelated to cystic fibrosis. Archivos de bronconeumologia 2013;49(10):415-20 doi: http://dx.doi.org/10.1016/j.ar-
bres.2013.01.012[published Online First: Epub Date]|.
31. Anwar GA, McDonnell MJ, Worthy SA, et al. Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study. Respiratory medicine 2013;107(7):1001-7 doi: http://dx.doi.org/10.1016/j.rmed.2013.04.013[published
Online First: Epub Date]|.
32. Chalmers JD, Goeminne P, Aliberti S, et al. The bronchiectasis severity index. An international derivation and validation study. American Journal of Respiratory & Critical Care Medicine 2014;189(5):576-85 doi: http://dx.doi.org/10.1164/rc-
cm.201309-1575OC[published Online First: Epub Date]|.
33. Rogers GB, Zain NM, Bruce KD, et al. A novel microbiota stratification system predicts future exacerbations in bronchiectasis. Annals of the American Thoracic Society 2014;11(4):496-503 doi: http://dx.doi.org/10.1513/AnnalsATS.201310-335OC[pub-
lished Online First: Epub Date]|.
34. Rajagopala S, Ramakrishnan A, Bantwal G, et al. Adrenal insufficiency in patients with stable non-cystic fibrosis bronchiectasis. Indian Journal of Medical Research 2014;139(3):393-401
35. de Camargo AA, Amaral TS, Rached SZ, et al. Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with noncystic fibrosis bronchiectasis. Archives of Physical Medicine & Rehabilitation 2014;95(5):892-9
doi: http://dx.doi.org/10.1016/j.apmr.2013.11.019[published Online First: Epub Date]|.
36. Martinez-Garcia MA, de Gracia J, Vendrell Relat M, et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. European Respiratory Journal 2014;43(5):1357-67 doi: http://dx.doi.org/10.1183/09031936.00026313[published
Online First: Epub Date]|.
37. McDonnell MJ, Jary HR, Perry A, et al. Non cystic fibrosis bronchiectasis: A longitudinal retrospective observational cohort study of Pseudomonas persistence and resistance. Respiratory medicine 2015;109(6):716-26 doi: 10.1016/j.rmed.2014.07.021[pub-
lished Online First: Epub Date]|.
38. Herrero-Cortina B, Vilaro J, Marti D, et al. Short-term effects of three slow expiratory airway clearance techniques in patients with bronchiectasis: a randomised crossover trial. Physiotherapy 2016;102(4):357-64 doi: 10.1016/j.physio.2015.07.005[pub-
lished Online First: Epub Date]|.
39. Guan WJ, Gao YH, Xu G, et al. Aetiology of bronchiectasis in Guangzhou, southern China. Respirology 2015;20(5):739-48 doi: 10.1111/resp.12528[published Online First: Epub Date]|.
40. Kadowaki T, Yano S, Wakabayashi K, et al. An analysis of etiology, causal pathogens, imaging patterns, and treatment of Japanese patients with bronchiectasis. Respiratory investigation 2015;53(1):37-44 doi: 10.1016/j.resinv.2014.09.004[published
Online First: Epub Date]|.
41. Amorim A, Bento J, Vaz AP, et al. Bronchiectasis: a retrospective study of clinical and aetiological investigation in a general respiratory department. Revista portuguesa de pneumologia 2015;21(1):5-10 doi: 10.1016/j.rppnen.2014.06.009[published Online
First: Epub Date]|.
42. Qi Q, Wang W, Li T, et al. Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population: A prospective study. Respirology 2015;20(6):917-24 doi: 10.1111/resp.12574[published Online First: Epub Date]|.
43. Maiz L, Vendrell M, Olveira C, et al. Prevalence and factors associated with isolation of Aspergillus and Candida from sputum in patients with non-cystic fibrosis bronchiectasis. Respiration; international review of thoracic diseases 2015;89(5):396-403 doi:
10.1159/000381289[published Online First: Epub Date]|.
44. Lonni S, Chalmers JD, Goeminne PC, et al. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Annals of the American Thoracic Society 2015;12(12):1764-70 doi: 10.1513/AnnalsATS.201507-472OC[published
Online First: Epub Date]|.
45. Gao YH, Guan WJ, Liu SX, et al. Aetiology of bronchiectasis in adults: A systematic literature review. Respirology 2016 doi: 10.1111/resp.12832[published Online First: Epub Date]|.
2014 [16] Belgium 245 68 Sputum 19% 8% 14% 15% 8% N/D 7% 11% N/D N/D N/D
2014 [17] Spain 819 59 Sputum 15% 32% 5% N/D N/D N/D 5% N/D 22%7 3% N/R N/R
2014 [18] UK 608 67 Sputum 29% 12% 7% 6% 10% N?D 7% N/D N/D Excluded 28%
2015 [19] UK and Spain 50 65 Sputum 20% 20% 6% 6% 10% 40%
2015 [20] UK 81 63 BAL 23% 5% 12% 8% 1% N/D 6% 1% ND 49%
2015 [21] China 144 45 Sputum 10% 31% 2% N/D N/D N/D 7% N/D N/D 40%
2015 [22] UK 155 61 Sputum8 57% 49% 20% 33% 25% N/D Not 10% 3% N/R
calculable
Exclusions: studies that were selective e.g studies of only positive cultures or only including P.aeruginosa or NTM patients; studies that did not report a full range of pathogens.
65
66
BTS Guideline
Appendix 7 (Continued )
References
1. Chan CH, Ho AK, Chan RC, et al. Mycobacteria as a cause of infective exacerbation in bronchiectasis. Postgraduate medical journal 1992;68(805):896-9
2. Nicotra MB, Rivera M, Dale AM, et al. Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort. Chest 1995;108(4):955-61
3. Evans SA, Turner SM, Bosch BJ, et al. Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. European Respiratory Journal 1996;9(8):1601-4
4. Wilson CB, Jones PW, O’Leary CJ, et al. Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. European Respiratory Journal 1997;10(8):1754-60
5. Cabello H, Torres A, Celis R, et al. Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. European Respiratory Journal 1997;10(5):1137-44
6. Ho PL, Chan KN, Ip MS, et al. The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis. Chest 1998;114(6):1594-8
7. Pasteur MC, Helliwell SM, Houghton SJ, et al. An investigation into causative factors in patients with bronchiectasis. American Journal of Respiratory and Critical Care Medicine 2000;162(4 pt1):1277-84
8. Angrill J, Agustí C, De Celis R, et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. American Journal of Respiratory and Critical Care Medicine 2001;164(9):1628-32
9. Palwatwichai A, Chaoprasong C, Vattanathum A, et al. Clinical, laboratory findings and microbiologic characterization of bronchiectasis in Thai patients. Respirology 2002;7(1):63-6
10. Angrill J, Agustí C, de Celis R, et al. Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors. Thorax 2002;57(1):15-19
11. King PT, Holdsworth SR, Freezer NJ, et al. Microbiologic follow-up study in adult bronchiectasis. Respiratory medicine 2007;101(8):1633-8
12. Steinfort DP, Brady S, Weisinger HS, et al. Bronchiectasis in Central Australia: a young face to an old disease. Respiratory medicine 2008;102(4):574-8
13. Murray MP, Pentland JL, Turnbull K, et al. Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis. European Respiratory Journal 2009;34(2):361-4 doi: http://dx.doi.org/10.1183/09031936.00163208[published Online First: Epub Date]|.
14. Ergan Arsava B, Coplu L. Does airway colonization cause systemic inflammation in bronchiectasis? Tuberkuloz ve Toraks 2011;59(4):340-7
15. Wong C, Jayaram L, Karalus N, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9842):660-7 doi: http://dx.doi.org/10.1016/S0140-
6736(12)60953-2[published Online First: Epub Date]|.
16. Goeminne PC, Nawrot TS, Ruttens D, et al. Mortality in non-cystic fibrosis bronchiectasis: a prospective cohort analysis. Respiratory medicine 2014;108(2):287-96 doi: http://dx.doi.org/10.1016/j.rmed.2013.12.015[published Online First: Epub Date]|.
17. Martinez-Garcia MA, de Gracia J, Vendrell Relat M, et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. European Respiratory Journal 2014;43(5):1357-67 doi: http://dx.doi.org/10.1183/09031936.00026313[published
Online First: Epub Date]|.
18. Chalmers JD, Goeminne P, Aliberti S, et al. The bronchiectasis severity index. An international derivation and validation study. American Journal of Respiratory & Critical Care Medicine 2014;189(5):576-85 doi: http://dx.doi.org/10.1164/rc-
cm.201309-1575OC[published Online First: Epub Date]|.
19. Sibila O, Suarez-Cuartin G, Rodrigo-Troyano A, et al. Secreted mucins and airway bacterial colonization in non-CF bronchiectasis. Respirology 2015;20(7):1082-8 doi: 10.1111/resp.12595[published Online First: Epub Date]|.
20. McDonnell MJ, Ahmed M, Das J, et al. Hiatal hernias are correlated with increased severity of non-cystic fibrosis bronchiectasis. Respirology 2015;20(5):749-57 doi: 10.1111/resp.12522[published Online First: Epub Date]|.
21. Guan WJ, Gao YH, Xu G, et al. Sputum bacteriology in steady-state bronchiectasis in Guangzhou, China. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
2015;19(5):610-9 doi: 10.5588/ijtld.14.0613[published Online First: Epub Date]|.
22. McDonnell MJ, Jary HR, Perry A, et al. Non cystic fibrosis bronchiectasis: A longitudinal retrospective observational cohort study of Pseudomonas persistence and resistance. Respiratory medicine 2015;109(6):716-26 doi: 10.1016/j.rmed.2014.07.021[-
published Online First: Epub Date]|.
Research Recommendation in Suggested Research Title: Patient Group Intervention Comparator Outcomes Why would this research
Guideline (e.g. What is the clinical and cost be important? (for the
effectiveness of…) public, patients or the
NHS)
Consensus criteria for diagnosis of ABPA Consensus criteria for diagnosis of
need to be validated in bronchiectasis ABPA need to be validated in bronchi-
cohorts. ectasis cohorts.
Consensus criteria for definition of abnormal Consensus criteria for definition of
post pneumococcal test immunisation abnormal post pneumococcal test im-
antibody responses need to be validated in munisation antibody responses need to
bronchiectasis cohorts. be validated in bronchiectasis cohorts.
Randomised controlled trials using clinically Does the effectiveness of airway clear- Patients with bronchiectasis and Airway clearance techniques Different severities of bron- Sputum production, Leicester Physiotherapy is time-con-
important outcome measures are required ance techniques differ according to the sputum production chiectasis (mild, moderate Cough Questionnaire (LCQ), suming and not always
to assess the effectiveness of airway severity of bronchiectasis? or severe) as assessed by quality of life (QOL), exercise enjoyable – patients may
clearance techniques in varying severities of severity scores capacity and exacerbation wish to be assured that the
bronchiectasis. frequency regime advised for them is
most appropriate for their
severity and likely benefits
Randomised controlled trials are required Is airway clearance useful for patients Patients with bronchiectasis and Airway clearance Usual care without airway Sputum production, LCQ, An increase or a change in
to evaluate the effects of airway clearance who are undergoing an exacerbation? sputum production during an clearance QOL, time to stable state, airway clearance is often
techniques in patients who are undergoing exacerbation time to next exacerbation, recommended during an
67
68
Appendix 8 (Continued )
Research Recommendation in Suggested Research Title: Patient Group Intervention Comparator Outcomes Why would this research
Guideline (e.g. What is the clinical and cost be important? (for the
effectiveness of…) public, patients or the
NHS)
Further interventional/randomised controlled Is there a role for “alternative therapy” Patients with bronchiectasis “Alternative therapies” Usual care Depending on the nature These modes of treatment
trials needed to establish the role of any al- in the management of bronchiectasis? of the therapy, may include are not currently funded due
BTS Guideline
ternative therapies in the management of sputum production, LCQ, to a lack of evidence but
bronchiectasis. QOL, spirometry, exercise some patients would value
capacity, BMI, exacerbation them if such evidence can
frequency, side-effects be found
Studies assessing the benefits of nutritional Are there benefits to nutritional Patients with bronchiectasis Nutritional supplementation Usual care without nutrition- BMI, severity scores, QOL, Poor nutrition contributes
supplementation in patients with bronchiec- supplementation in patients with al supplementation exacerbation frequency, to severity of disease – can
tasis should be undertaken. bronchiectasis? exercise capacity, spirometry this be addressed?
The role of education, self management What are the educational needs of Patients with bronchiectasis Education on aspects of Usual care without edu- QOL, psychological wellbe- Disease-specific education
plans and who delivers the pulmonary patients with bronchiectasis and how the disease and self-care, cation ing, use of medical services, may improve QOL for these
rehabilitation needs to be explored. should this education be delivered? delivered in various ways e.g. exacerbation frequency. patients and potentially
face to face, online reduce use of healthcare
resources
The role of education, self management Are self management plans useful in Patients with bronchiectasis who Personalised self-manage- Usual care without a QOL, use of medical services, This is a simple tool to
plans and who delivers the pulmonary the management of bronchiectasis exacerbate ment plan delivered by a self-management plan exacerbation frequency, improve outcomes
rehabilitation needs to be explored. exacerbations? healthcare provider who is hospital admissions
familiar with the patient’s
case
The role of pulmonary rehabilitation after Is there a benefit from early pulmonary Bronchiectasis patients admitted Post-discharge pulmonary Usual care QOL, exercise capacity, This has been demonstrated
exacerbations requiring hospital admission rehabilitation after exacerbations for an exacerbation rehabilitation commencing spirometry, time to full to be useful in patients with
needs to be explored. of bronchiectasis requiring hospital within 2 weeks resolution, time to next COPD. Although bronchiec-
admission? exacerbation, readmission tasis patients don’t admit at
rate within 30 days and the same rate as COPD, the
within 90 days ones that require admission
for exacerbations are most
likely to be high consumers
of healthcare resource
The incidence of cross-infection of respiratory What is the incidence of cross-infection Patients with bronchiectasis un- Those exercising in a group Those exercising at home Microbiological evidence of In cystic fibrosis, cross-infec-
pathogens in the group exercise setting of respiratory pathogens in a group dergoing pulmonary rehabilitation setting cross infection and/or rates tion is known to occur, but it
should be investigated in the bronchiectasis exercise setting? of cross infection has not yet been reported in
population. bronchiectasis patients. The-
oretically a group exercise
setting would be high risk
as exercise would tend to
encourage expectoration.
A randomised control trial of P. aeruginosa Does P. aeruginosa eradication therapy Bronchiectasis patients with new Eradication therapy according Placebo treatment Microbiological outcomes, There is no direct evidence
eradication therapy is needed to determine prevent long term colonisation or P. aeruginosa infection to the 2018 BTS bronchiecta- side effects/drop-out rates, for this form of treatment
the microbiological and clinical outcomes of improve health outcomes? sis guideline symptom, QOL, LCQ, time but it is widely used, incur-
eradication therapy. to next exacerbation, ring expense and potential
spirometry, exercise capacity, side-effects. If it is effective,
hospital admissions/use of it could make a significant
other healthcare resources difference to patient out-
comes which are adversely
affected by P. aeruginosa
colonisation.
69
Notes
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